[3] 5-'GH'-3-((4-'GH'piperazin-1-yl)methyl)-1H-indole by Asch

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References

Synthesize Find similar Stage #1: With trimethyl orthoformate

1 h; Stage #2: With sodium cyanoborohydride; acetic acid

0.166667 h; Stage #3: With tri-isopropylsilane; ethane-1,2dithiol; trifluoroacetic acid in water 2 h;

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Rx-ID: 9116846 Find similar reactions

Mutulis, Felikss; Mutule, Ilze; Lapins, Maris; Wikberg, Jarl E.S.

Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 7 p. 1035 - 1038 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 22949101 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ; Title/Abstract Full Text Show Details

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Rx-ID: 31808201 Find similar reactions

With sodium tris(acetoxy)borohydride; acetic acid in dichloromethane

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Na, Young Min

Bulletin of the Korean Chemical Society, 2011 , vol. 32, # 1 p. 307 - 310 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar Multi-step reaction with 2 steps 1: trichlorophosphate 2: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane View Scheme

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Rx-ID: 31808264 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2011 , vol. 32, # 1 p. 307 - 310 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 45401610 Find similar reactions

90%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

General procedure: The gramine (2 mmol) and the corresponding amine (2–10 mmol) were dissolved in drytoluene (15 ml), and the mixture was refluxed for 8–14 h and monitored by TLC. The solventwas condensed subsequently in vacuo to obtain crude products which was purified bycolumn chromatography on silica gel using Et2NH/MeOH/CHCl3 (2/4/94–3/5/92, v/v/v). A

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Rx-ID: 4923624 Find similar reactions

With potassium tert-butylate in tetrahydrofuran

2 h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

Love, Brian E.; Nguyen, Binh T.

Synlett, 1998 , # 10 p. 1123 - 1125 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 6169023 Find similar reactions

Orth et al.

Journal of Pharmaceutical Sciences, 1968 , vol. 57, p. 1814,1815 Full Text View citing articles Show Details

Inst. Luso Farmaco

Patent: GB1075156 , 1963 ; Chem.Abstr., 1968 , vol. 68, # 69041k Full Text Show Details

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Rx-ID: 22957393 Find similar reactions

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75%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in dichloromethane

T=25 - 30°C; 1 h; Hide Experimental Procedure

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ; Title/Abstract Full Text Show Details

151:Description 151 (D151) 3- (4-METHYLPIPERAZIN-1-YLMETHYL)-1 H-INDOLE

Description 151 (D151) 3- (4-METHYLPIPERAZIN-1-YLMETHYL)-1 H-INDOLE In a three necked round bottom flask equipped with pressure equalizing funnel, indole (1.17 g, 0.01 mole) and dichloromethane (8 mL) were taken. 1-METHYLPIPERAZINE (1. 01G, 0.011 moles) and formaldehyde (9 mL, 0.012 mole) was added slowly at room temperature and the reaction mixture was stirred well for one hour. After the completion of reaction (TLC), the product was isolated by distillation under reduced pressure. The residue was extracted with ethyl acetate (2 x 25 mL). The combined organic extracts were washed with water, followed by brine, dried over anhydrous sodium sulfate. The organic layer was evaporated under vacuum. The residue could either be an oily liquid or solid mass. The oily mass was triturated with n-hexane to obtain a solid material. The solid obtained was identified by IR, NMR and mass spectral analyses.

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Nirogi, Ramakrishna; Shinde, Anil; Kambhampati, Rama Sastry; Mohammed, Abdul Rasheed; Saraf, Sangram Keshari; Badange, Rajesh kumar; Bandyala, Thrinath Reddy; Bhatta, Venugopalarao; Bojja, Kumar; Reballi, Veena; Subramanian, Ramkumar; Benade, Vijay; Palacharla, Raghava Choudary; Bhyrapuneni, Gopinadh; Jayarajan, Pradeep; Goyal, Vinod; Jasti, Venkat

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 22984287 Find similar reactions

With lithium aluminium tetrahydride in tetrahydrofuran

4 - 9 h; Heating / reflux; Hide Experimental Procedure

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 56 ; Title/Abstract Full Text Show Details

188:Description 188 (D188) 3- (4-METHYLPIPERAZIN-1-YLMETHYL)-1 H-INDOLE (ALSO, D151)

Description 188 (D188) 3- (4-METHYLPIPERAZIN-1-YLMETHYL)-1 H-INDOLE (ALSO, D151) (1H-Indol-3-yl)- (4-methylpiperazin-1-yl) methanone (2.44 g, 0.01 moles) in THF was treated with cooled and stirred suspension of Lithium aluminum hydride (g, 0. 011 MOLES in THF slowly over the period of 2 to 5 hours, the reaction mixture was heated to reflux for 2 - 4 hours, after the completion of reaction, the reaction mixture was poured on to the ice and the compound was extracted in ethyl acetate. The residue obtained was purified by flash chromatography (silica gel, ETOAC/HEXANES, 2/8) to afford the compound, which was identified by IR, NMR and mass spectral analyses as the title compound.

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Rx-ID: 45401611 Find similar reactions

92%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 5940307 Find similar reactions

/BRN= 618828/ (4), LiAlH4;

Glamkowski et al.

Journal of Medicinal Chemistry, 1977 , vol. 20, p. 1485 Full Text View citing articles Show Details

entspr. NO-Verb., Red.;

Hoechst

Patent: FR2272673DE2522143 , 1975 ; Chem.Abstr., vol. 84, # 90183 Full Text Show Details

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Rx-ID: 45401612 Find similar reactions

93%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 5942470 Find similar reactions

Gramin, N-Nitroso-piperazin;

Glamkowski et al.

Journal of Medicinal Chemistry, 1977 , vol. 20, p. 1485 Full Text View citing articles Show Details

entspr. NH-Verb., Acylierung;

Hoechst

Patent: FR2272673DE2522143 , 1975 ; Chem.Abstr., vol. 84, # 90183 Full Text Show Details

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Rx-ID: 25271575 Find similar reactions

in toluene

Hide Experimental Procedure

American Hoechst Corporation

Patent: US3997539 A1, 1976 ; Title/Abstract Full Text Show Details

3.a:3-(4-Aminopiperazin-1-yl) methylindole

a. A mixture of 34.8 g (0.22 mol) of gramine and 23.9 g (0.20 mol) of nitrosopiperazine in 700 ml. of toluene is refluxed while stirring under nitrogen for 48 hours. The reaction solution is then concentrated under reduced pressure until a precipitate appears and then is cooled to 0° C. and is filtered. The product is washed with cold toluene and dried to produce crystals of 3-(4-nitrosopiperazin-1-yl)methylindole. This product is recrystallized from toluene to yield pure plates, m.p. 116°-118° C. Analysis: Calculated for C13 H16 N4 O: 63.92percent C; 6.60percent H; 22.93percent N Found: 63.84percent C; 6.64percent H; 23.06percent N.

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86%

With hydrazine hydrate in methanol

T=20°C; Reflux; Hide Experimental Procedure

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Rx-ID: 46083507 Find similar reactions

Phoenix Molecular Designs; DUNN, Sandra E.; JAYANTHAN, Aarthi; NAGIREDDY, Jaipal Reddy; ANNEDI, Subhash; VAN DRIE, John H.; DAYNARD, Timothy S.; HUYNH, My-my

Patent: US2017/240549 A1, 2017 ; Location in patent: Paragraph 0665; 0666 ; Title/Abstract Full Text Show Details

3.A:

A. A solution of 3-((4-methylpiperazin-1-yl)methyl)-5-nitro-1H-indole (compound 3a, 0.25 g, 0.911 mmol) in MeOH (10 mL) was treated with Raney-Nickel (˜50 mg) followed by hydrazine hydrate (0.44 mL, 9.113 mmol) at room temperature. The reaction was refluxed for 10-15 minutes in a pre-heated oil bath and then brought back to room temperature. The solution was filtered through a pad of celite and washed with methanol (2*15 mL). The combined methanol layer was evaporated and crude was purified by flash column chromatography (2M NH3 in MeOH:CH2Cl2, 5:95) on silica gel to obtain 3-((4-methylpiperazin-1-yl)methyl)-1H-indol-5-amine, compound 3b, (0.19 g, 86percent) as a tan solid.

57%

With palladium on activated carbon; hydrogen in ethanol

T=20°C; 6 h; Hide Experimental Procedure

Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang

European Journal of Medicinal Chemistry, 2017 , vol. 139, p. 492 - 502 Title/Abstract Full Text View citing articles Show Details

4.1.7. General procedure for preparation of intermediates 10a and10b

General procedure: At room temperature, palladium on charcoal (10percent w/w) wasadded to a solution of intermediates (9a and 9b, 1.8 mmol) inethanol. The reaction mixture was hydrogenated for 6 h. When TLC showed the completion of the reaction, the catalyst was filtered off.The filtrate was evaporated to give the desired intermediates.

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Multi-step reaction with 2 steps 1: acetic acid / 35 °C 2: palladium on activated carbon; hydrogen / ethanol / 6 h / 20 °C View Scheme

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Rx-ID: 46330277 Find similar reactions

Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang

European Journal of Medicinal Chemistry, 2017 , vol. 139, p. 492 - 502 Title/Abstract Full Text View citing articles Show Details

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Multi-step reaction with 2 steps 1: acetic acid / 35 °C 2: palladium on activated carbon; hydrogen / ethanol / 6 h / 20 °C View Scheme

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Rx-ID: 46330351 Find similar reactions

Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang

European Journal of Medicinal Chemistry, 2017 , vol. 139, p. 492 - 502 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 30048782 Find similar reactions

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44%

With acetic acid in 1,4dioxane; water

T=20°C; Mannich reaction;

Soubhye, Jalal; Prevost, Martine; Van Antwerpen, Pierre; Zouaoui Boudjeltia, Karim; Rousseau, Alexandre; Furtmueller, Paul G.; Obinger, Christian; Vanhaeverbeek, Michel; Ducobu, Jean; Neve, Jean; Gelbcke, Michel; Dufrasne, Francois

Journal of Medicinal Chemistry, 2010 , vol. 53, # 24 p. 8747 - 8759 Title/Abstract Full Text View citing articles Show Details

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-fluoro-1H-indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 39008284 Find similar reactions

65%

With acetic acid in ethanol; isopropyl alcohol

T=20°C; Mannich Aminomethylation; Hide Experimental Procedure

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Hamann, Anton R.; De Kock, Carmen; Smith, Peter J.; Van Otterlo, Willem A.L.; Blackie, Margaret A.L.

Bioorganic and Medicinal Chemistry Letters, 2014 , vol. 24, # 23 p. 5466 - 5469 Title/Abstract Full Text View citing articles Show Details

3-{[4-(prop-2-yn-1-yl)piperazine-1-yl]methyl}-1H-indole (14)

1-(Prop-2-yn-1-yl)piperazine 8 (0.19 g, 1.5 mmol) and indole (0.15 g, 1.3 mmol) were dissolved inEtOH:i-PrOH (8 mL, 1:1). Formaldehyde (0.1 mL, 37 percent, 1.9 mmol) and acetic acid (0.02 mL, 0.4 mmol)were then added in that respective order. The solution was then stirred overnight at rt, followed by concentration and diluting with EtOAc (20 mL). The solution was washed with diluted NaOH (15 mL) and the aqueous layer was washed with EtOAc (20 mL). The organic layers were pooled, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Purification was done using 9:1DCM:MeOH as eluent to offer the product as white solid (0.21 g, 65 percent yield).

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Rx-ID: 33537471 Find similar reactions

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84%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

General procedure: Indole (3mmol), formaldehyde (1.2mmol), and secondary amine (3mmol), mL were mixed in reaction flask and then add distill water 10–15 and refluxed the solution for 2h with vigorous stirring. The reaction completion was checked by TLC, and the resulting solid mixture was then filter. In some cases solid mixture was not formed so it was extracted with ethyl acetate, purified by column chromatography using acetone and hexane system in 1:1 ratio, and pure product is obtained in 75–89percent yield [37].

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Rx-ID: 33869989 Find similar reactions

72%

in ethanol; water

T=20°C; Mannich reaction;

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Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 45401618 Find similar reactions

97%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 45401617 Find similar reactions

93%

in toluene

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen,

Reflux; Hide Experimental Procedure

Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 45401615 Find similar reactions

80%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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resp. Phenylhydrazon, H2SO4;

Rx-ID: 6101539 Find similar reactions

Inst. Luso Farmaco

Patent: GB1075156 , 1963 ; Chem.Abstr., 1968 , vol. 68, # 69041k Full Text Show Details

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Rx-ID: 22949100 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ;

Title/Abstract Full Text Show Details

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Rx-ID: 40275635 Find similar reactions

Multi-step reaction with 2 steps 1.1: acetic acid / water / 5 - 20 °C / |Large scale 1.2: 3 h / 15 - 30 °C / |Large scale 2.1: methanol / 8 - 35 °C / |Large scale View Scheme

SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Rama Sastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: WO2015/83179 A1, 2015 ;

Multi-step reaction with 2 steps 1.1: water / 0.5 h / 5 - 20 °C / |Large scale 1.2: 0.5 h / 10 - 20 °C / |Large scale 1.3: 3 h / 15 - 30 °C / |Large scale 2.1: water; methanol / 8 - 35 °C / |Large scale View Scheme

SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Rama Sastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: US2016/297759 A1, 2016 ;

Title/Abstract Full Text Show Details

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Rx-ID: 40275640 Find similar reactions

56.6%

in methanol; water

T=8 - 35°C; Large scale; Hide Experimental Procedure

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SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Rama Sastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: US2016/297759 A1, 2016 ; Location in patent: Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026-0037 ; Title/Abstract Full Text Show Details

1.ii; 1.iii; 1.iv:

10020] Simultaneously in a separate reactor 125 Kg of methanol was charged at 25-35° C. 5-methoxyindole (20 Kg, 0.1359 Kg Mole) was added and the mass was stirred to obtain a clear solution. The mass was cooled to 8° C.-i0° C. in 1.5 hours by circulating brine in the reactor jacket. The Maimich adduct, prepared as above, was charged into the reactor containing cooled methanolic solution of 5-methoxyindole from an addition tank over a period of50-60 minutes, while maintaining the temperature of the reaction mass at 8° C.-16° C. After completion of addition, the mass temperature was allowed to rise to 20° C.-35° C. Then the reaction mass was further stirred for 3 hours at 20° C.-35° C. Afier completion of the reaction (thin layer chromotography), the reaction mass was discharged into clean and dry containers.10021] Another reactor was charged with 400 L of demineralised water followed by the addition of 20 Kg of lye solution at 20° C.-35° C. The content was cooled to 10° C.-15° C. under stirring. The above reaction mass in the containers was added to the reactor, maintaining the mass temperature at 10° C.-15° C. in 30-40 minutes. The final pH of the solution was adjusted to 9-12, if necessary by adding some more lye solution. Then the product was extracted with ethyl acetate (1x260 L & 4x160 L) maintaining the mass temperature at 10° C-i 5° C. during the entire operations. The pH of aqueous layer was adjusted to 9-12 before each extraction.10022] The combined organic layer was washed with (2x 170 Kg) of brine solution (the brine solution was prepared by adding 95 Kg of vacuum salt to 245 Kg of demineralised water) at 20° C.-35° C. The total organic extracts, obtained afier the brine washing, were dried over 35 Kg of anhydrous sodium sulfate under stirring for 30 minutes at 20° C.-35° C.10023] The organic layer was filtered and charged into another clean reactot The solvent was removed totally under 500-600 mm of Hg vacuum, at 20° C.-45° C.10024] The residual mass, thus obtained, was cooled to room temperature and charged 60 L toluene and stirred the contents at 20° C.-45° C. for 15 minutes. The solvent was distilled oil under reduced pressure (500-700 mm of Hg vacuum) at 45-65° C. The operation was repeated again by the addition of 60 L toluene and stirring the contents at 20° C.-45° C. for 15 mm. The solvent was distilled off under reduced pressure (500-700mm of Hg vacuum) at 45-65° C. again to ensure total removal of ethylacetate to avoid losses during recrystallization step. The residual tecimical product, 5-methoxy-3-[(4-methyl-i piperazinyl)methyl] -1 H-indole, thus obtained, was recrystallized twice, as per the details given below, to obtain the product of desired purity.Step (iii): Crystallization of 5-methoxy-3-[(4- methyl-i -piperazinyl)methyl]- 1 Hindole10025] Charged 61 Kg of toluene into the above reactor which contains the tecimical product, 5-methoxy-3-[(4- methyl-i -piperazinyl)methyl] -i H-indole. The contents wereheated to 85-95° C. and maintained for an hour at 85-95° C. The clear solution, thus obtained, was allowed to cool to 30° C.-40° C. by circulating room temperature water in the reactor jacket. The mass was further cooled to 10° C.-i5° C. and maintained for 3 hours at the same temperature. The crystalline solid mass was filtered through nutsche and the solid on the nutsche was washed with 18 L of chilled (10° C.-i5° C.) toluene and sucked well. The material was further washed with 20 L of n-hexane and sucked dry to obtain 22.7 Kg of crystalline material.Step (iv): Recrystallization of 5-methoxy-3-[(4- methyl-i -piperazinyl)methyl]- 1 H-indole10026] Charged 40 Kg of toluene into a reactor followedby the addition of the 5-methoxy-3-[(4-methyl-i -piperazinyl)methyl]-iH-indole (22.7 Kg) obtained in the first crystallization step under stirring. The contents were heated to95-105° C. and maintained for 2 hours to obtain a clearsolution. The mass was allowed to cool to 35° C.-40° C. bycirculating room temperature water in the jacket. It wasfurther cooled to 10° C.-i5° C. and maintained for 3 hoursat 10° C.-i5° C. The crystalline solid mass was filteredthrough nutsche and the solid on the nutsche was washedwith 8 L of chilled (10° C.-i5° C.) toluene and sucked well.The material was further washed with 15 L of n-hexane andsucked dry. The material was further dried in tray driers at20° C.-25° C. to obtain the title product, as off whitecrystalline powdet10027] Weight of the crystallized material: 19.95 Kg;10028] Yield (based on 5-methoxyindole charged): 56.6percent;10029] HPLC purity: 99.74percent;10030] Total impurities: 0.26percent;10031] Assay: 100.6percent;10032] Moisture content: 0.24percent;10033] Melting range (° C.): 139-140.6;10034] IR spectra (cm’): 3125, 2951, 1875, 1622, 1585,1492, 1351, 1288, 1215, 1059, 930, 654;10035] ‘H-NMR (CDC13, ö ppm): 2.30 (3H, s), 2.5 (8H,bs), 3.71 (2H, s), 3.86 (3H, s), 6.83-6.86 (iH, dd, J=8.8i, 2.7Hz), 7.01 (iH, d, J=2.06 Hz), 7.18-7.20 (2H, m), 8.91 (iH,s);10036] ‘3C-NMR (CDC13, ö ppm): 45.89, 52.79, 53.39,55.11, 55.83, 101.3, 111.39, 111.75, 111.81, 124.88, 128.45,131.48, 153.77;10037] Mass [M+H]: 260.3.

in methanol

T=8 - 35°C; Large scale; Hide Experimental Procedure

SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Rama Sastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: WO2015/83179 A1, 2015 ; Location in patent: Page/Page column 4; 6; 7 ; Title/Abstract Full Text Show Details

1.ii:Step (ii):

Step (ii): Simultaneously in a separate reactor 125 Kg of methanol was charged at 25 °C - 35 °C. 5-methoxyindole (20 Kg, 0.1359 Kg Mole) was added and the mass was stirred to obtain a clear solution. The mass was cooled to 8 °C - 10 °C in 1.5 hours by circulating brine in the reactor jacket. The Mannich adduct, prepared as above, was charged into the reactor containing cooled methanolic solution of 5-methoxyindole from an addition tank over a period of 50 - 60 minutes, while maintaining the temperature of the reaction mass at 8 °C - 16 °C. After completion of addition, the mass temperature was allowed to rise to 20 °C - 35 °C. Then the reaction mass was further stirred for 3 hours at 20 °C - 35 °C. After completion of the reaction (thin layer chromtography), the reaction mass was discharged into clean and dry containers.Another reactor was charged with 400 L of demineralised water followed by the addition of 20 Kg of lye solution at 20 °C - 35 °C. The content was cooled to 10 °C - 15 °C under stirring. The above reaction mass in the containers was added to the reactor, maintaining the mass temperature at 10 °C - 15 °C in 30 - 40 minutes. The final pH of the solution was adjusted to 9 - 12, if necessary by adding some more lye solution. Then the product was extracted with ethyl acetate (1 x 260 L & 4 x 160 L) maintaining the mass temperature at 10 °C - 15 °C during the entire operations. The pH of aqueous layer was adjusted to 9 - 12 before each extraction.The combined organic layer was washed with (2 x 170 Kg) of brine solution (the brine solution was prepared by adding 95 Kg of vacuum salt to 245 Kg of demineralised water) at 20 °C - 35 °C. The total organic extracts, obtained after the brine washing, were dried over 35 Kg of anhydrous sodium sulfate under stirring for 30 minutes at 20 °C - 35 °C.The organic layer was filtered and charged into another clean reactor. The solvent was removed totally under 500 - 600 mm of Hg vacuum, at 20 °C - 45 °C.The residual mass, thus obtained, was cooled to room temperature and charged 60 L toluene and stirred the contents at 20 °C - 45 °C for 15 minutes. The solvent was distilled off under reduced pressure (500 - 700 mm of Hg vacuum) at 45 °C - 65 °C. The operation was repeated again by the addition of 60 L toluene and stirring the contents at 20 °C - 45 °C for 15 min. The solvent was distilled off under reduced pressure (500 - 700 mm of Hg vacuum) at 45 °C - 65 °C again to ensure total removal of ethylacetate to avoid losses during recrystallization step. The residual technical product, 5-methoxy-3-[(4-methyl-lpiperazinyl)methyl]-lH-indole, thus obtained, was recrystallized twice, as per the details given below, to obtain the product of desired purity.

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Rx-ID: 44823198 Find similar reactions

62%

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-methoxylindole in methanol; water

T=5 - 30°C; Mannich Aminomethylation; 3 h;

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 45401613 Find similar reactions

83%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 22949099 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ;

Title/Abstract Full Text Show Details

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Rx-ID: 44823189 Find similar reactions

Stage #1: 1-methyl-piperazine;

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Nirogi, Ramakrishna; Shinde, Anil; Kambhampati, Rama Sastry; Mohammed, Abdul Rasheed; Saraf, Sangram Keshari; Badange, Rajesh kumar;

formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-chloro-1H-indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

Bandyala, Thrinath Reddy; Bhatta, Venugopalarao; Bojja, Kumar; Reballi, Veena; Subramanian, Ramkumar; Benade, Vijay; Palacharla, Raghava Choudary; Bhyrapuneni, Gopinadh; Jayarajan, Pradeep; Goyal, Vinod; Jasti, Venkat

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33537473 Find similar reactions

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85%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

Stage #1: 4-ethylpiperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-methoxylindole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 45401614 Find similar reactions

85%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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5-Nitro-indol, Formaldehyd, NMethyl-piperazin, wss. Essigsaeure, Mannich-Rk. nach Meth. v. G. Cavallini, F. Ravenna, Farmaco (Pavia), Ed. Sci. 13 (1958) 105;

Rx-ID: 6837769 Find similar reactions

DeGraw; Brown; Skinner

Journal of medicinal chemistry, 1966 , vol. 9, # 1 p. 140 - 142 Title/Abstract Full Text View citing articles Show Details

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52; 56 ;

Title/Abstract Full Text Show Details

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Rx-ID: 44823214 Find similar reactions

51%

With acetic acid

T=35°C; Mannich Aminomethylation; Hide Experimental Procedure

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Qin, Mingze; Tian, Ye; Sun, Xiaoqing; Yu, Simiao; Xia, Juanjuan; Gong, Ping; Zhang, Haotian; Zhao, Yanfang

European Journal of Medicinal Chemistry, 2017 , vol. 139, p. 492 - 502 Title/Abstract Full Text View citing articles Show Details

4.1.9. General procedure for preparation of intermediates 13a, 13e,and 13g

General procedure: To a mixture of intermediate 12 (6.2 mmol), paraformaldehyde(9.3 mmol) in acetic acid (5 mL) was added appropriate secondaryamine (9.3 mmol). The mixture was stirred at 35° C for 5-8 h andwas monitored by TLC. The solution was alkalized with aqueousNaOH to pH 8-9, and was extracted with dichloromethane. Theorganic phase was concentrated to give a residue, which was purifiedby column chromatography (CH2Cl2/MeOH, 100/1 to 75/1) toprovide the desired intermediates.

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-nitroindole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 44823216 Find similar reactions

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-methylthio-1H-indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33537476 Find similar reactions

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87%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 10085377 Find similar reactions

45%

With acetic acid in 1,4dioxane; water

T=20°C; Mannich reaction;

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Lindquist, Charlotta; Ersoy, Oguz; Somfai, Peter

Tetrahedron, 2006 , vol. 62, # 14 p. 3439 - 3445 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 44823206 Find similar reactions

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-isopropoxy-1H-indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 4512029 Find similar reactions

in toluene

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Kulagowski, Janusz J.; Broughton, Howard B.; Curtis, Neil R.; Mawer, Ian M.; Ridgill, Mark P.; Baker, Raymond; Emms, Frances; Freedman,

Stephen B.; Marwood, Rosemarie; Patel, Shil; Patel, Smita; Ragan, C. Ian; Leeson, Paul D.

Journal of Medicinal Chemistry, 1996 , vol. 39, # 10 p. 1941 - 1942 Title/Abstract Full Text View citing articles Show Details

Heating;

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Rx-ID: 6175006 Find similar reactions

Indol, CH2O/1-Phenylpiperazin;

Sterling Drug Inc.

Patent: GB944443 , 1959 ; Chem.Abstr., 1964 , vol. 60, # 9293g Full Text Show Details

Indol, Formalin/1-Phenylpiperazin;

Sterling Drug Inc.

Patent: US3135794 , 1964 ; Chem.Abstr., 1964 , vol. 61, # 4374g Full Text Show Details

resp. Phenylhydrazon, H2SO4;

Inst. Luso Farmaco

Patent: GB1075156 , 1963 ; Chem.Abstr., 1968 , vol. 68, # 69041k Full Text Show Details

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Rx-ID: 9577765 Find similar reactions

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76%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

45%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

35%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

Hide Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 22949105 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52-53 ;

Title/Abstract Full Text Show Details

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Rx-ID: 9577768 Find similar reactions

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50%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

25%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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resp. Phenylhydrazon, H2SO4;

Rx-ID: 6117594 Find similar reactions

Inst. Luso Farmaco

Patent: GB1075156 , 1963 ; Chem.Abstr., 1968 , vol. 68, # 69041k Full Text Show Details

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resp. Phenylhydrazon, H2SO4;

Rx-ID: 6116496 Find similar reactions

Inst. Luso Farmaco

Patent: GB1075156 , 1963 ; Chem.Abstr., 1968 , vol. 68, # 69041k Full Text Show Details

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Rx-ID: 33869990 Find similar reactions

36%

in ethanol; water

T=20°C; Mannich reaction;

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Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33869992 Find similar reactions

68%

in ethanol; water

T=20°C; Mannich reaction;

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Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 22949098 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ;

Title/Abstract Full Text Show Details

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Rx-ID: 44823193 Find similar reactions

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-bromo-1H-indole in methanol; water

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Rx-ID: 33537475 Find similar reactions

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84%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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N-4-Fluorphenylpiperazin, CH2O, Indol;

Rx-ID: 6177987 Find similar reactions

Centre Europeen de Recherches Mauvernay

Patent: GB1116196 , 1966 ; Chem.Abstr., 1968 , vol. 69, # 87017g Full Text Show Details

Mauvernay; Busch

Patent: US3453366 , 1966 ; Chem.Abstr., 1969 , vol. 71, # 70636b Full Text Show Details

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Rx-ID: 33307383 Find similar reactions

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63%

in ethanol; water

T=20°C;

Yarim, Mine; Koksal, Meric; Schepmann, Dirk; Wuensch, Bernard

Chemical Biology and Drug Design, 2011 , vol. 78, # 5 p. 869 - 875 Title/Abstract Full Text View citing articles Show Details

63%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 33869995 Find similar reactions

58%

in ethanol; water

T=20°C; Mannich reaction;

Synthesize Find similar

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 44823184 Find similar reactions

Stage #1: formaldehyd; 1-t-

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Nirogi, Ramakrishna; Shinde, Anil; Kambhampati, Rama Sastry; Mohammed, Abdul Rasheed; Saraf, Sangram Keshari; Badange, Rajesh kumar;

Butoxycarbonylpiperazine With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 45401619 Find similar reactions

96%

in toluene

Reflux; Hide Experimental Procedure

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Yin, Xiu-Juan; Huang, Xiao-Yan; Ma, Yun-Bao; Geng, Chang-An; Li, Tian-Ze; Chen, Xing-Long; Yang, Tong-Hua; Zhou, Jun; Zhang, Xue-Mei; Chen, Ji-Jun

Journal of Asian Natural Products Research, 2017 , vol. 19, # 6 p. 610 - 622 Title/Abstract Full Text View citing articles Show Details

4.2.3. General procedure for preparation of compounds 3–18 and 20–24

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Rx-ID: 8742471 Find similar reactions

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78%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

50%

With acetic acid in dichloromethane

T=20°C; Mannich reaction; 6 h;

Huebner; Kraxner; Gmeiner

Journal of Medicinal Chemistry, 2000 , vol. 43, # 23 p. 4563 - 4569 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33869996 Find similar reactions

48%

in ethanol; water

T=20°C; Mannich reaction;

Synthesize Find similar

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 33537480 Find similar reactions

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83%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 33869997 Find similar reactions

55%

in ethanol; water

T=20°C; Mannich reaction;

Synthesize Find similar

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 9577803 Find similar reactions

Synthesize Find similar

75%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

30%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

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3-N'-Benzyl-piperazinomethyl-5nitro-indol, H2 (Pd), A.;

Rx-ID: 6839116 Find similar reactions

DeGraw; Brown; Skinner

Journal of medicinal chemistry, 1966 , vol. 9, # 1 p. 140 - 142 Title/Abstract Full Text View citing articles Show Details

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(yield)65percent;

DeGraw; Brown; Skinner

Journal of medicinal chemistry, 1966 , vol. 9, # 1 p. 140 - 142 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 9577773 Find similar reactions

25%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Synthesize Find similar

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 22949102 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52 ;

Title/Abstract Full Text Show Details

Synthesize Find similar

Rx-ID: 33537474 Find similar reactions

Synthesize Find similar

85%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

22%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 33869994 Find similar reactions

37%

in ethanol; water

T=20°C; Mannich reaction;

Synthesize Find similar

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 33537472 Find similar reactions

Synthesize Find similar

85%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 22949107 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 52-53 ;

Title/Abstract Full Text Show Details

Synthesize Find similar

Rx-ID: 4512547 Find similar reactions

in toluene

Heating;

Synthesize Find similar

Kulagowski, Janusz J.; Broughton, Howard B.; Curtis, Neil R.; Mawer, Ian M.; Ridgill, Mark P.; Baker, Raymond; Emms, Frances; Freedman, Stephen B.; Marwood, Rosemarie; Patel, Shil; Patel, Smita; Ragan, C. Ian; Leeson, Paul D.

Journal of Medicinal Chemistry, 1996 , vol. 39, # 10 p. 1941 - 1942 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 9577772 Find similar reactions

Synthesize Find similar

47%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

20%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

Synthesize Find similar

Rx-ID: 9610655 Find similar reactions

Synthesize Find similar

26%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

20%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Malinka, Wieslaw; Swiatek, Piotr

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33869991 Find similar reactions

21%

in ethanol; water

T=20°C; Mannich reaction;

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Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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1-<(Pyrrolidinylcarbonyl)methyl>piperazin, Indol, Trioxymethylen;

Rx-ID: 6131334 Find similar reactions

Delalande

Patent: DE2128520 ; Chem.Abstr., 1972 , vol. 76, # 72554a Full Text Show Details

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Rx-ID: 44823209 Find similar reactions

Stage #1: 1-methyl-piperazine; formaldehyd With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-(2,2,2trifluoroethoxy)indole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 9577802 Find similar reactions

30%

in acetic acid

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Malinka, Wieslaw; Swiatek, Piotr

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T=20°C; Mannich reaction; 3 h;

Acta Poloniae Pharmaceutica - Drug Research, 2004 , vol. 61, # 2 p. 107 - 111 Title/Abstract Full Text View citing articles Show Details

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Acetylindol, Formaldehyd, Phenylpiperazin;

Rx-ID: 5900903 Find similar reactions

Sterling Drug Inc.

Patent: US3328407 , 1966 ; Chem.Abstr., vol. 68, # 49652 Full Text Show Details

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Rx-ID: 33537483 Find similar reactions

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84%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 8742476 Find similar reactions

48%

With acetic acid in dichloromethane

T=20°C; Mannich reaction; 6 h;

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Huebner; Kraxner; Gmeiner

Journal of Medicinal Chemistry, 2000 , vol. 43, # 23 p. 4563 - 4569 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 5949170 Find similar reactions

Entspr. NH-Verb., Acyl.;

Hoechst

Patent: FR2272673DE2522143 , 1975 ; Chem.Abstr., vol. 84, # 90183 Full Text Show Details

Amin 7, PhCOCl, NaOH;

Glamkowski et al.

Journal of Medicinal Chemistry, 1977 , vol. 20, p. 1485 Full Text View citing articles Show Details

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Hide Experimental Procedure

Rx-ID: 29067405 Find similar reactions

Laboratorios Del. Dr. Esteve, S.A.

Patent: EP2149373 A1, 2010 ; Title/Abstract Full Text Show Details

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Some of the compounds identified as 5HT7 ligands with good affinity by the method above described are specified in the following list: a. 3-(2-aminoethyl)-N,N-dimethyl-1 H-indole-5-sulfonamide b. 1-((6-chloropyridin-3-yl)methyl)-4-(2-isopropoxyphenyl)piperazine c. 3-((4-(2-ethoxyphenyl)piperazin-1-yl)methyl)-1H-indole d. 3-(4-(2-methoxyphenyl)piperazin-1-yl)-1-phenylpropan-1-ol e. 1-(4-(1H-imidazol-1-yl)benzyl)-4-(2-isopropoxyphenyl)piperazine f. N-(2,3-dihydro-1H-inden-5-yl)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propanamide g. 4-(4-(5-isopropyl-2-methoxybenzyl)piperazin-1-yl)-1H-indole h. 1-(1-(3,4-difluorobenzyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one i. 1-(1-(2-phenoxyethyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one ...

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Rx-ID: 36054899 Find similar reactions

66%

in acetic acid

T=0°C; 1 h; Hide Experimental Procedure

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Abdelfattah, Mohamed A.O.; Lehmann, Jochen; Abadi, Ashraf H.

Bioorganic and Medicinal Chemistry Letters, 2013 , vol. 23, # 18 p. 5077 - 5081 Title/Abstract Full Text View citing articles Show Details

Procedure forthe preparation of 3-[4-Phenylpiperazin-1-ylmethyl]-1H-indole derivatives

10 mmol (1.17 gm) of indoletogether with 10 mmol of the corresponding phenyl piperazine free base and 15mL of HCHO 37percent were mixed with 5 mL glacial acetic acid at 0Oc for 1hour. The mixture was then alkalinized with 5M NaOH and extracted twice with 30mL diethyl ether. The combined organic layers were dried over anhydrous Na2SO4and evaporated under reduced pressure. The crude residue was then subjected toSilica gel column chromatography eluting with CH2Cl2:MeOH 9.5: 0.5. 4Yield: (2.2 gm, 66percent);m.p.: 52- 54 oC; 1HNMR (CDCl3): 1.36 (t, 3H, J= 7Hz,-OCH2CH3), 3.15 (brs, 4H, 2 X –CH2, piperazine), 3.23 (brs, 4H, 2 X –CH2,piperazine), 4.0 (q, 2H, J= 7Hz, 2H, -OCH2CH3), 4.41 (s, 2H, -CH2-), 6.77- 6.96(m, 4H, Aromatic), 7.09- 7.16 (m, 2H, Aromatic), 7.26- 7.56 (m, 3H, Aromatic),8.78 (s, 1H, NH); GC/MS: m/z 335 (M+, 5percent), 206 (40percent), 164 (70percent), 120 (100percent), 77(60percent); CHN: for C21H25N3O calcd. C 75.19, H7.51, N 12.53 ; found C 74.63; H 7.80; N 12.97.

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Rx-ID: 33869993 Find similar reactions

52%

in ethanol; water

T=20°C; Mannich reaction;

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Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 40641135 Find similar reactions

With sodium cyanoborohydride; acetic acid in N,N-dimethyl acetamide

T=50°C; 0.166667 h; Flow reactor;

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Rodrigues, Tiago; Hauser, Nadine; Reker, Daniel; Reutlinger, Michael; Wunderlin, Tiffany; Hamon, Jacques; Koch, Guido; Schneider, Gisbert

Angewandte Chemie - International Edition, 2015 , vol. 54, # 5 p. 1551 - 1555 Angew. Chem., 2015 , vol. 127, # 5 p. 1571 - 1575,5 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33307380 Find similar reactions

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23%

in ethanol; water

T=20°C;

Yarim, Mine; Koksal, Meric; Schepmann, Dirk; Wuensch, Bernard

Chemical Biology and Drug Design, 2011 , vol. 78, # 5 p. 869 - 875 Title/Abstract Full Text View citing articles Show Details

23%

in ethanol; water

T=20°C; Mannich reaction;

Akkoc, Meric Koeksal; Yueksel, Mine Yarim; Durmaz, Irem; Atalay, Renguel Ecetin

Turkish Journal of Chemistry, 2012 , vol. 36, # 4 p. 515 - 525 Title/Abstract Full Text View citing articles Show Details

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With lithium aluminium

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Rx-ID: 2990860 Find similar reactions

Golubev, V. E.; Trubitsyna, T. K.; Mashkovskii, M. D.; Suvorov, N. N.

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tetrahydride in tetrahydrofuran

3 h; Heating;

Pharmaceutical Chemistry Journal, 1981 , vol. 15, # 2 p. 88 - 90 Khimiko-Farmatsevticheskii Zhurnal, 1981 , vol. 15, # 2 p. 30 - 33 Title/Abstract Full Text View citing articles Show Details

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Multi-step reaction with 2 steps 1: 49.5 percent / N,N'dicyclohexylcarbodiimide / CHCl3 / 24 h / 20 °C 2: LiAlH4 / tetrahydrofuran / 3 h / Heating View Scheme

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Rx-ID: 20379696 Find similar reactions

Golubev, V. E.; Trubitsyna, T. K.; Mashkovskii, M. D.; Suvorov, N. N.

Pharmaceutical Chemistry Journal, 1981 , vol. 15, # 2 p. 88 - 90 Khimiko-Farmatsevticheskii Zhurnal, 1981 , vol. 15, # 2 p. 30 - 33 Title/Abstract Full Text View citing articles Show Details

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Multi-step reaction with 2 steps 1: 49.5 percent / N,N'dicyclohexylcarbodiimide / CHCl3 / 24 h / 20 °C 2: LiAlH4 / tetrahydrofuran / 3 h / Heating View Scheme

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Rx-ID: 20384285 Find similar reactions

Golubev, V. E.; Trubitsyna, T. K.; Mashkovskii, M. D.; Suvorov, N. N.

Pharmaceutical Chemistry Journal, 1981 , vol. 15, # 2 p. 88 - 90 Khimiko-Farmatsevticheskii Zhurnal, 1981 , vol. 15, # 2 p. 30 - 33 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 16327 Find similar reactions

With benzene

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Runti; Orlando

Annali di Chimica (Rome, Italy), 1953 , vol. 43, p. 308,312 Full Text View citing articles Show Details

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Rx-ID: 16354 Find similar reactions

With ethanol; sodium ethanolate

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Runti; Orlando

Annali di Chimica (Rome, Italy), 1953 , vol. 43, p. 308,312 Full Text View citing articles Show Details

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Rx-ID: 16375 Find similar reactions

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Akkerman; Veldstra

Recueil des Travaux Chimiques des Pays-Bas, 1954 , vol. 73, p. 629,646 Full Text View citing articles Show Details

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Find similar Rx-ID: 1495308 Find similar reactions

77.5%

in ethanol

24 h; Heating;

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Afsah, El-Sayed M.; Jackson, Anthony H.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984 , # 8 p. 1929 - 1932 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 5563984 Find similar reactions

Gramin, Piperazin, Δ;

Kamal et al.

Pakistan Journal of Scientific and Industrial Research, 1966 , vol. 9, # 4 p. 323,324, 325 Chem.Abstr., 1969 , vol. 71, # 3199y Full Text Show Details

Gramin, Piperazin;

Kamal et al.

Pakistan Journal of Scientific and Industrial Research, 1966 , vol. 9, # 4 p. 323,324, 325 Chem.Abstr., 1969 , vol. 71, # 3199y Full Text Show Details

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Multi-step reaction with 2 steps 1.1: acetic acid / water / 0.67 h / 25 °C 1.2: 1.5 h / 25 - 30 °C 2.1: methanol / 2 h / 20 - 30 °C View Scheme

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Rx-ID: 42124437 Find similar reactions

SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Ramasastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: WO2016/27276 A1, 2016 ; Title/Abstract Full Text Show Details

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Rx-ID: 42124443 Find similar reactions

96%

in methanol

T=20 - 30°C; 2 h; Hide Experimental Procedure

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SUVEN LIFE SCIENCES LIMITED; NIROGI, Ramakrishna; KAMBHAMPATI, Ramasastri; SHINDE, Anil Karbhari; JASTI, Venkateswarlu

Patent: WO2016/27276 A1, 2016 ; Location in patent: Page/Page column 10; 11; 12 ; Title/Abstract Full Text Show Details

1.ii.iii:Preparation of 3-[(1-t-Butyloxycarbonyl piperazin-4-yl)methyI]-5-methoxy-1H-indole

5-Methoxyindole (106.4 grams, 0.7238 moles) and methanol (550 mL) were charged into a 4 necked round bottom flask. The mass was stirred for 10 minutes at 25 °C to obtain a clear solution and then cooled the mass to 18 - 20 °C. The mannich adduct (prepared in above step) was added to the flask through an addition funnel maintaining mass temperature below 20 °C, over a period of 1 hour. The mass was further stirred for a period of 1 hour at 25 - 30 °C, while monitoring the progress of the reaction by thin layer chromatography (TLC).After completion of the reaction (1 hour), DM water (2.2 Litres) and ethyl acetate (1Litre) were added to the reaction mass and pH adjusted to 10.5 (on pH paper) with lye solution (80 mL) maintaining the mass temperature at 20 - 24 °C. The organic (product) layer was separated and the aqueous layer was further extracted with ethyl acetate (2 x 500 mL). The combined organic layer was washed with saturated brine solution (300 mL) and dried over anhydrous sodium sulfate. The organic layer was filtered free of sodium sulfate and concentrated under reduced pressure. n-Hexane (300 mL) was added to the residual mass and further concentrated under vacuum for removal of traces of ethyl acetate to obtain 272.2 grams of technical product.Purity: 96.16 percent; - NMR (CDC13, δ ppm): 1.45 (9H, s), 2.44 (4H, bm), 3.41 - 3.43 (4H, bm), 3.69 (2H, s), 3.87 (3H, s), 6.85 - 6.88 (1H, dd, J = 8.75, 2.23 Hz), 7.10 ( 1 H, d, J = 0.96 Hz), 7.19 (1 H, d, J = 2.24 Hz), 7.24 - 7.26 (1H, d), 8.04 (1H, bs);Mass [M+H]+: 346.2. Step (iii): Purification of 3-[(l-t-Butyloxycarbonyl piperazin-4-yl)methyI]-5-methoxy-lH- indole n-Hexane (1.25 Litres) was taken in 2 Litres four necked round bottom flask equipped with thermometer pocket and mechanical stirrer and charged the above obtained technical compound (270.9 grams). The mass was stirred for 1 hour at 25 °C. The product was filtered through Buckner funnel under vacuum. The compound was washed with n-hexane (2 x 125 mL), sucked well and air dried at 25 °C for 20 hours to obtain 240.0 grams of above title compound. Yield: 96 percent; Purity: 97.09 percent; - NMR (CDCI3, δ ppm): 1.45 (9H, s), 2.45 (4H, s), 3.43 (4H, s), 3.69 (2H, s), 3.86 (3H, s), 6.85 - 6.88 (1H, dd, J = 8.7, 2.2 Hz), 7.08 - 7.09 (1H, d, J = 1 .57 Hz), 7.19 ( 1 H, d, J = 2.2 Hz), 7.23 - 7.25 (l H, d, J = 8.77 Hz), 8.25 (lH, bs); - Mass [M+H]+: 346.2.

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Rx-ID: 44823202 Find similar reactions

Stage #1: formaldehyd; 1-tButoxycarbonylpiperazine With acetic acid in water

T=10 - 30°C; Mannich Aminomethylation; 2 h; Stage #2: 5-methoxylindole in methanol; water

T=5 - 10°C; Mannich Aminomethylation; 3 h;

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Journal of Medicinal Chemistry, 2017 , vol. 60, # 5 p. 1843 - 1859 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 33537482 Find similar reactions

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88%

in water

Mannich reaction; 2 h; Reflux;

Khan, Khalid Mohammed; Rahim, Fazal; Ambreen, Nida; Taha, Muhammad; Iqbal, Sarosh; Haider, Syed Moazzam; Perveen, Shahnaz

Journal of the Chemical Society of Pakistan, 2012 , vol. 34, # 3 p. 748 - 757 Title/Abstract Full Text View citing articles Show Details

in water

2 h; Reflux; Hide Experimental Procedure

Mesaik, M. Ahmed; Khan, Khalid Mohammed; Rahim, Fazal; Taha, Muhammad; Haider, Syed Moazzam; Perveen, Shahnaz; Khalid, Ahmed Shukralla; Abdalla, Omer M.; Soomro, Samreen; Voelter, Wolfgang

Bioorganic Chemistry, 2015 , vol. 60, p. 118 - 122 Title/Abstract Full Text View citing articles Show Details

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Rx-ID: 8996753 Find similar reactions

79%

in toluene

4 h; Heating;

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Moll, Annette; Huebner, Harald; Gmeiner, Peter; Troschuetz, Reinhard

Bioorganic and medicinal chemistry, 2002 , vol. 10, # 6 p. 1671 - 1679 Title/Abstract Full Text View citing articles Show Details

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Find similar Rx-ID: 10103878 Find similar reactions

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33%

in ethanol

Mannich reaction; 18 h; Heating;

Smid, Pieter; Coolen, Hein K. A. C.; Keizer, Hiskias G.; Van Hes, Rolf; De Moes, Jan-Peter; Den Hartog, Arnold P.; Stork, Bob; Plekkenpol, Rob H.; Niemann, Leonarda C.; Stroomer, Cees N. J.; Tulp, Martin Th. M.; Van Stuivenberg, Herman H.; McCreary, Andrew C.; Hesselink, Mayke B.; Herremans, Arnoud H. J.; Kruse, Chris G.

Journal of Medicinal Chemistry, 2005 , vol. 48, # 22 p. 6855 - 6869 Title/Abstract Full Text View citing articles Show Details

33%

in ethanol; water

18 h; Heating / reflux; Hide Experimental Procedure

SOLVAY PHARMACEUTICALS B.V.

Patent: US2006/122175 A1, 2006 ; Location in patent: Page/Page column 4 ; Title/Abstract Full Text Show Details

Example 2; Syntheses of Specific Compounds Compounds Prepared as Described in Scheme (see below) 1; 3-[4-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl-methyl]-1H-indole (compound 5a).; A solution of compound 2a (2.2 g, 8.5 mmol), indole (1 g, 8.5 mmol) and formaldehyde (37percent, 0.7 ml) in ethanol (30 ml) was refluxed for 18 hours. The mixture was allowed to cool to room temperature and was concentrated in vacuo to give crude compound 5a as a brown oil, which was purified by silica gel column chromatography (EtOAc/methanol, 95/5, v/v). Compound 5a was obtained as a white solid (850 mg, 33percent); mp 85-86° C.; 1HNMR (400 MHz, DMSO-d6): δ 10.8 (s, 1H, NH-indole); 7.65 (d, 1H, J=8 Hz, H-arom); 7.35 (d, 1H, J=8 Hz, H-arom); 7.18 (d, 1H, J=2 Hz, H2-indole); 7.07 (t, 1H, J=7 Hz, H-arom); 6.98 (t,1H, J=7 Hz, H-arom); 6.67 (t,1H, J=7 Hz, H-arom); 6.4-6.48 (2.x. d, 2H, H-arom); 4.2 (bm, 4H, OCH2CH2O); 3.7 (bs, 2H, CH2); 3.0, 2.55 (2.x. bs, 8H, piperazine). HRMS (C21H24N3O2) [M+H]+: found m/z350.1899, calculated 350.1869.