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

Page 1

Reaxys

PubChem

eMolecules

Bioactivities (401)

Yield

LabNetwork

SigmaAldrich

Reactions (276)

Conditions

Substances (252)

Targets (66)

Citations (72)

References

100

Synthesize Find similar

Rx-ID: 22949123 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

Patent: WO2004/48330 A1, 2004 ; Location in patent: Page 55 ; Title/Abstract Full Text Show Details

101


Synthesize Find similar

Rx-ID: 6845820 Find similar reactions

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

DeGraw; Brown; Skinner

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

(yield)9percent;

DeGraw; Brown; Skinner

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

102

Synthesize Find similar

Rx-ID: 8742473 Find similar reactions

52%

With acetic acid in dichloromethane

T=20°C; Mannich reaction; 6 h;

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar

Huebner; Kraxner; Gmeiner

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

103

Synthesize Find similar

Rx-ID: 8742474 Find similar reactions

51%

104

With acetic acid in dichloromethane

T=20°C; Mannich reaction; 6 h;

Synthesize Find similar

Synthesize Find similar

Huebner; Kraxner; Gmeiner

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

Synthesize Find similar


Synthesize Find similar

Rx-ID: 22949104 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

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

Title/Abstract Full Text Show Details

105

Synthesize Find similar

Rx-ID: 33537481 Find similar reactions

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar

80%

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

5:

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].

106


Synthesize Find similar

Rx-ID: 5950905 Find similar reactions

Amin 7, p-Fluor-benzoylchlorid, NEt3;

Glamkowski et al.

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

Entspr. NH-Verb., Acyl.;

Hoechst

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

107

Synthesize Find similar

Rx-ID: 9577804 Find similar reactions

20%

in acetic acid

T=20°C; Mannich reaction; 3 h;

Synthesize Find similar

Synthesize Find similar

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

108

Synthesize Find similar

Rx-ID: 36054896 Find similar reactions

58%

in acetic acid

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

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar

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

General procedure: 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:(2.1 gm, 58percent); m.p.: 49-51 oC; 1HNMR (CDCl3):2.06 (brs, 4H, 2 X –CH2, piperazine), 2.28 (brs, 4H, 2 X –CH2,

piperazine),3.84 (s, 2H, -CH2-), 6.93- 7.79 (m, 8H, Aromatic), 8.24 (brs, 1H, NH); GC/MS:m/z 360 (M+, 5percent), 206 (40percent), 231 (80percent), 120 (100percent), 77 (40percent); CHN: for C19H19Cl2N3calcd. C 63.34, H 5.32, N 11.66 ; found C 63.73; H 5.65; N 12.01.


109

Synthesize Find similar

Rx-ID: 40641134 Find similar reactions

in water; acetonitrile

0.266667 h;

Synthesize Find similar

Synthesize Find similar

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

110

Synthesize Find similar

Rx-ID: 33537477 Find similar reactions

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar

81%

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

5:

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].

111


Synthesize Find similar

Rx-ID: 22949106 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

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

Title/Abstract Full Text Show Details

112

Synthesize Find similar

Rx-ID: 33307381 Find similar reactions

Synthesize Find similar

Synthesize Find similar

20%

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

20%

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

113

Synthesize Find similar

Multi-step reaction with 2 steps 1.1: potassium carbonate / acetonitrile / 30 - 80 °C 2.1: acetic acid / 1,2-dichloro-ethane / 6 h / 30 °C / |Molecular sieve 2.2: 6 h / 0 - 30 °C View Scheme

Synthesize Find similar

Rx-ID: 43099939 Find similar reactions

Jeankumar, Variam Ullas; Reshma, Rudraraju Srilakshmi; Vats, Rahul; Janupally, Renuka; Saxena, Shalini; Yogeeswari, Perumal; Sriram, Dharmarajan

European Journal of Medicinal Chemistry, 2016 , vol. 122, p. 216 - 231 Title/Abstract Full Text View citing articles Show Details


114

Synthesize Find similar

Rx-ID: 43100020 Find similar reactions

60.5%

Synthesize Find similar

Stage #1: With acetic acid in 1,2-dichloro-ethane

T=30°C; 6 h; Molecular sieve; Stage #2: With sodium tris(acetoxy)borohydride in methanol

T=0 - 30°C; 6 h; Hide Experimental Procedure

Synthesize Find similar

Jeankumar, Variam Ullas; Reshma, Rudraraju Srilakshmi; Vats, Rahul; Janupally, Renuka; Saxena, Shalini; Yogeeswari, Perumal; Sriram, Dharmarajan

European Journal of Medicinal Chemistry, 2016 , vol. 122, p. 216 - 231 Title/Abstract Full Text View citing articles Show Details

4.1.7 General procedure for the synthesis of N-alkyl derivatives (22 & 23)

General procedure: To a solution of 7-chloro-4-(piperazin-1-yl)quinoline (1mmol) in dry dichloroethane (6mL) was added the corresponding aldehyde (1.1mmol), freshly activated 3Å molecular sieves (0.25g) and catalytic amount of acetic acid. The reaction mixture was stirred at 30°C for 6h and filtered through celite bed (under N2 atmosphere). The solvent was removed under reduced pressure and residue further diluted with dry methanol (6mL) and cooled to 0°C. Sodium triacetoxy borohydride (1.5mmol) was added (portion-wise) and the reaction was stirred at 30°C for 6h (monitored by TLC & LCMS for completion for completion). The solvent was then removed under reduced pressure and the residue diluted with water (5mL) and extracted with dichloromethane (10mL). The aqueous phase was back-extracted with dichloromethane (2×10mL) and dried over sodium sulphate. The combined organic phases were concentrated under reduced and residue purified by column chromatography using hexane: ethylacetate as eluent to give the desired product in good yield. 4.1.7.1 4(4-((1H-Indol-3-yl)methyl)piperazin-1-yl)-7-chloroquinoline (22) The compound was synthesized according to the above general procedure using 7-chloro-4-(piperazin-1-yl)quinoline (0.25g, 1mmol), indole-2carboxaldehyde (0.16g, 1.1mmol), to afford 22 (0.23g, 60.5percent) as buff coloured solid. 1H NMR (DMSO-d6): δH. 2.59–2.64 (m, 2H), 3.12–3.19 (m, 4H), 3.56 (s, 2H), 7.06–8.63 (m, 10H), 9.78 (bs, 1H). 13C NMR

(DMSO-d6): δC. 155.9, 152.5, 149.6, 136.9, 133.4, 129.9, 128.6, 127.5, 125.7, 122.8, 122.3, 121.4, 119.3, 118.2, 111.9, 110.7, 109.8, 55.6, 51.8, 43.2. ESI-MS m/z 377.2 (M+H)+. Anal Calcd for C22H21ClN4; C, 70.11; H, 5.62; N, 14.87; Found C, 70.19; H, 5.67; N, 14.91.

115

Synthesize Find similar

Rx-ID: 40641137 Find similar reactions

13%

116

Synthesize Find similar

With sodium tris(acetoxy)borohydride in 1,2-dichloro-ethane

T=20°C; 24 h;

Synthesize Find similar

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


Synthesize Find similar

Rx-ID: 27873942 Find similar reactions

JANSSEN PHARMACEUTICA N.V.

Patent: WO2008/109333 A1, 2008 ; Location in patent: Page/Page column 55 ;

Title/Abstract Full Text Show Details

117

Synthesize Find similar

Rx-ID: 28548905 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 196 ;

Title/Abstract Full Text Show Details

118

Synthesize Find similar

Rx-ID: 8742475 Find similar reactions

76%

With acetic acid in dichloromethane

T=20°C; Mannich reaction; 6 h;

Synthesize Find similar

Synthesize Find similar

Huebner; Kraxner; Gmeiner

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

Synthesize Find similar


119

Synthesize Find similar

Rx-ID: 40641136 Find similar reactions

Multi-step reaction with 2 steps 1: sodium cyanoborohydride; acetic acid / N,N-dimethyl acetamide / 0.17 h / 50 °C / |Flow reactor 2: water; acetonitrile / 0.27 h View Scheme

Synthesize Find similar

Synthesize Find similar

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

120

Synthesize Find similar

Rx-ID: 40641142 Find similar reactions

in water; acetonitrile

0.266667 h;

Synthesize Find similar

Synthesize Find similar

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

121

Synthesize Find similar

Rx-ID: 45401616 Find similar reactions

70%

in toluene

10 h; Reflux; Hide Experimental Procedure

Synthesize Find similar

Synthesize Find similar

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

4.2.4. General procedure for preparation of compound 19

The gramine (4 mmol) and 2-amino-ethyl-piperazine (2 mmol) were dissolved in dry toluene(15 ml). The mixture were refluxed for 10 h monitored by TLC. The solvent was removedin vacuo to afford crude products which were purified by column chromatography on silicagel using Et2NH /MeOH/CHCl3 (3:5: 92, v/v/v).N-[N-(3-Indolylmethyl)-aminoethyl]-N-piperazinyl-3-indolylmethylamine (19): Yellowoil, yield 70percent. 1H NMR (400 MHz, CDCl3) δH: 8.88 (s, 1H, NH), 8.85 (s, 1H, NH), 7.72-7.01(m, 10H, H-2, 2′, 4, 4′, 5, 5′, 6, 6′, 7, 7′), 3.98 (s, 2H, CH2 N), 3.72 (s, 2H, CH2CH2NHCH2),2.80–2.28 (m, 13H, 2-aminoethylpiperazinyl-H). 13C NMR (100 MHz, CDCl3) δ: 136.4(C-8, 8′), 128.1 (C-9), 127.0 (C-9′), 124.1 (C-2), 122.8 (C-2′), 122.0 (C-6), 121.8 (C-6′),119.4 (C-5), 119.4 (C-5′), 118.7 (C-4, 4′), 114.5 (C-3), 111.9 (C-3′), 111.3 (C-7), 111.1 (C-7′),57.4 (CH2 N), 53.1 (C3″, 5″), 53.0 (CH2 N), 52.7 (C-2″, 6″), 45.6 (CH2CH2NHCH2), 44.5(CH2CH2NHCH2). ESIMS: m/z 388 [M + H]+; HRESIMS: m/z 388.2477 [M + H]+ (calcdfor C24H29N5, 388.2496).

122

Synthesize Find similar

Rx-ID: 33537479 Find similar reactions

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar

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

5:

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].

123

Synthesize Find similar

Rx-ID: 23457135 Find similar reactions

OTSUKA PHARMACEUTICAL CO., LTD.

Patent: EP1555267 A1, 2005 ; Location in patent: Page/Page column 394 ; Title/Abstract Full Text Show Details


124

Synthesize Find similar

Rx-ID: 22949103 Find similar reactions

SUVEN LIFE SCIENCES LIMITED

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

Title/Abstract Full Text Show Details

125

Synthesize Find similar

Rx-ID: 33537478 Find similar reactions

78%

in water

Mannich reaction; 2 h; Reflux;

Synthesize Find similar

Synthesize Find similar

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

126

Synthesize Find similar

Synthesize Find similar

Rx-ID: 28548921 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 206 ; Title/Abstract Full Text Show Details


127

Synthesize Find similar

Rx-ID: 28549175 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 133 ;

Title/Abstract Full Text Show Details

128

Synthesize Find similar

Rx-ID: 29685540 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BRADBURY, Robert, Hugh; CARR, Gregory, Richard; RABOW, Alfred, Arthur; RAO KORUPOJU, Srinivasa; TUMMA, Harikrishna

Patent: WO2010/92371 A1, 2010 ; Location in patent: Page/Page column 102-103 ;

Title/Abstract Full Text Show Details

129

Synthesize Find similar

Rx-ID: 28548917 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 206 ; Title/Abstract Full Text Show Details


130

Synthesize Find similar

Hide Experimental Procedure

Rx-ID: 25383100 Find similar reactions

Eisai Co., Ltd.

Patent: EP1254895 A1, 2002 ; Title/Abstract Full Text Show Details

5:Example 5

Example 5 1-[(4-Cyano-5-methyl-4-phenyl)hexyl]-4-[(3-indolyl)methyl]piperazine The title compound was obtained as a pale yellow oil in accordance with the method of Example 3 (76percent). Further, the hydrochloride of the title compound was obtained in a conventional method. Free body: 1H-NMR (400MHz, CDCl ) δ 0.76 (d, J = 6.8Hz, 3H), 1.04-1.18 (m, 1H), 1.18 (d, J = 6.8Hz, 3H), 1.47-1.60 (m, 1H), 1.86 (dt, J = 4.4Hz, J = 12.4Hz, 1H), 2.03-2.16 (m, 2H), 2.22-2.32 (m, 2H), 2.33 (bs, 4H), 2.49 (bs, 4H), 3

3.70 (s, 2H), 7.05-7.20 (m, 4H), 7.23-7.48 (m, 5H), 7.70 (d, J = 6.8Hz, 1H), 8.25-8.40 (m, 1H). Hydrochloride: ESI-Mass; 415 (MH+)

131

Synthesize Find similar

Rx-ID: 28548918 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 206 ;

Title/Abstract Full Text Show Details

132

Synthesize Find similar

Rx-ID: 28548915 Find similar reactions


ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 205 ;

Title/Abstract Full Text Show Details

133

Synthesize Find similar

Hide Experimental Procedure

Rx-ID: 23882886 Find similar reactions

Li, Qun; Woods, Keith W.; Zhu, Gui-Dong; Fischer, John P.; Gong, Jianchun; Li, Tongmei; Gandhi, Virajkumar; Thomas, Sheela A.; Packard, Garrick K.; Song, Xiaohong; Abrams, Jason N.; Diebold, Robert B.; Dinges, Jurgen; Hutchins, Charles W.; Stoll, Vincent S.; Rosenberg, Saul H.; Giranda, Vincent L.

Patent: US2003/199511 A1, 2003 ; Location in patent: Page/Page column 44 ; Title/Abstract Full Text Show Details

130:6-(5-(4-(1H-Indol-3-ylmethyl)-piperazin-1-yl)-pyridin-3-yl)-isoquinoline

EXAMPLE 130 6-(5-(4-(1H-Indol-3-ylmethyl)-piperazin-1-yl)-pyridin-3-yl)-isoquinoline The title compound was prepared by substituting Example 124 for aniline, and 3-formylindole for Example 116A in example 116B. MS (ESI) (m/z 420M+H)+; 1H NMR (400 MHz, DMSO-D6) δ ppm 1.89 (s, 2H) 2.50 (m, 4H) 2.60 (m, 4H) 7.02 (m, 2H) 7.27 (d, J=2.46 Hz, 1H) 7.36 (d, J=7.98 Hz, 1H) 7.68 (m, 2H) 7.87 (d, J=5.83 Hz, 1H) 8.05 (dd, J=8.59, 1.53 Hz, 1H) 8.22 (d, J=8.90 Hz, 1H) 8.34 (m, 2H) 8.44 (d, J=1.84 Hz, 1H) 8.54 (d, J=5.83 Hz, 1H) 9.35 (s, 1H) 10.93 (s, 1H).

134

Synthesize Find similar

Hide Experimental Procedure

Synthesize Find similar

Rx-ID: 23928857 Find similar reactions

Li, Qun; Woods, Keith W.; Zhu, Gui-Dong; Fischer, John P.; Gong, Jianchun; Li, Tongmei; Gandhi, Virajkumar; Thomas, Sheela A.; Packard, Garrick K.; Song, Xiaohong; Abrams, Jason N.; Diebold, Robert; Dinges, Jurgen; Hutchins, Charles; Stoll, Vincent S.; Rosenberg, Saul H.; Giranda, Vincent L.

Patent: US2003/187026 A1, 2003 ; Title/Abstract Full Text Show Details

130:6-(5-(4-(1H-Indol-3-ylmethyl)-piperazin-1-yl)-pyridin-3-yl)-isoquinoline

EXAMPLE 130 6-(5-(4-(1H-Indol-3-ylmethyl)-piperazin-1-yl)-pyridin-3-yl)-isoquinoline The title compound was prepared by substituting Example 124 for aniline, and 3-formylindole for Example 116A in example 116B. MS (ESI) (m/z 420M+H)+; 1H NMR (400 MHz, DMSO-D6) δ ppm 1.89 (s, 2H) 2.50 (m, 4H) 2.60 (m, 4H) 7.02 (m, 2H) 7.27 (d, J=2.46 Hz, 1H) 7.36 (d, J=7.98 Hz, 1H) 7.68 (m, 2H) 7.87 (d, J=5.83 Hz, 1H) 8.05 (dd, J=8.59, 1.53 Hz, 1H) 8.22 (d, J=8.90 Hz, 1H) 8.34 (m, 2H) 8.44 (d, J=1.84 Hz, 1H) 8.54 (d, J=5.83 Hz, 1H) 9.35 (s, 1H) 10.93 (s, 1H).


135

Synthesize Find similar

Rx-ID: 29685541 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BRADBURY, Robert, Hugh; CARR, Gregory, Richard; RABOW, Alfred, Arthur; RAO KORUPOJU, Srinivasa; TUMMA, Harikrishna

Patent: WO2010/92371 A1, 2010 ; Location in patent: Page/Page column 102-103 ;

Title/Abstract Full Text Show Details

136

Synthesize Find similar

Rx-ID: 5954000 Find similar reactions

Amin 7, /BRN= 403117/, NEt3;

Glamkowski et al.

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

Entspr. NH-Verb., Acyl.;

Hoechst

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

137

Synthesize Find similar

Rx-ID: 28548909 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 204 ;


Title/Abstract Full Text Show Details

138

Synthesize Find similar

Rx-ID: 29685542 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED; BRADBURY, Robert, Hugh; CARR, Gregory, Richard; RABOW, Alfred, Arthur; RAO KORUPOJU, Srinivasa; TUMMA, Harikrishna

Patent: WO2010/92371 A1, 2010 ; Location in patent: Page/Page column 102-103 ;

Title/Abstract Full Text Show Details

139

Synthesize Find similar

Rx-ID: 46083498 Find similar reactions

85%

Synthesize Find similar

With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine in N,N-dimethylformamide

T=20°C; 4 h; Hide Experimental Procedure

Synthesize Find similar

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; 0667 ; Title/Abstract Full Text Show Details

3.B:

B. A solution of 3-((4-methylpiperazin-1-yl)methyl)-1H-indol-5-amine (compound 3b, 0.175 g, 0.716 mmol), 1-benzyl-1H-pyrazole-4-carboxylic acid (compound 1c, 0.16 g, 0.787 mmol) and Et3N (0.2 mL, 1.432 mmol) in dry DMF (5 mL) was treated with HBTU (0.27 g, 0.716 mmol) at room temperature and stirred for 4 h. The reaction was diluted with 1N NaOH solution (50 mL), water (50 mL) and product was extracted into ethyl acetate (2*50 mL). The combined ethyl acetate layer was washed with brine (50 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2M NH3 in MeOH:CH2Cl2, 2:98 to 5:95) on silica gel to obtain 1-benzyl-N-(3-((4-methylpiperazin-1-yl)methyl)-1H-indol-5-yl)-1H-pyrazole-4carboxamide, compound No.3, (0.26 g, 85percent) as a pale yellow solid. 1H NMR (DMSO-d6) δ 2.21 (s, 3H), 2.25-2.40 (m, 8H), 3.55 (s, 2H), 5.39 (s, 2H), 7.19 (d, 1H, J=1.2 Hz), 7.27-7.39 (m, 7H), 7.83 (s, 1H), 8.06 (s, 1H), 8.41 (s, 1H), 9.69 (s, 1H), 10.85 (s, 1H); ESI-MS (m/z, percent): 429 (MH+, 100percent).


140

Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 2 steps 1: hydrazine hydrate / methanol / 20 °C / Reflux 2: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine / N,N-dimethyl-formamide / 4 h / 20 °C View Scheme

Rx-ID: 46083508 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 ; Title/Abstract Full Text Show Details

141

Synthesize Find similar

Rx-ID: 28548911 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 204 ;

Title/Abstract Full Text Show Details

142

Synthesize Find similar

Rx-ID: 10786688 Find similar reactions

SCHERING CORPORATION

Patent: WO2007/126964 A2, 2007 ; Location in patent: Page/Page column 100 ; Title/Abstract Full Text Show Details


143

Synthesize Find similar

Rx-ID: 9180861 Find similar reactions

70%

Synthesize Find similar

With sodium tris(acetoxy)borohydride in 1,2-dichloro-ethane

Synthesize Find similar

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

144

Synthesize Find similar

Multi-step reaction with 5 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl4 / dioxane / 24 h / Heating 5: 70 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14560971 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

145

Synthesize Find similar

Multi-step reaction with 3 steps 1: 79 percent / xylene / 96 h / Heating 2: 69 percent / TiCl4 / dioxane / 24 h / Heating 3: 70 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14562106 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details


146

Synthesize Find similar

Multi-step reaction with 4 steps 1: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 2: 79 percent / xylene / 96 h / Heating 3: 69 percent / TiCl4 / dioxane / 24 h / Heating 4: 70 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14562162 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

147

Synthesize Find similar

Multi-step reaction with 5 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl4 / dioxane / 24 h / Heating 5: 70 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14567978 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

148

Synthesize Find similar

Multi-step reaction with 2 steps 1: 69 percent / TiCl4 / dioxane / 24 h / Heating 2: 70 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14578296 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details


149

Synthesize Find similar

Multi-step reaction with 3 steps 1.1: dichloromethane / 1 h / Inert atmosphere 1.2: 48 h / 20 °C / Inert atmosphere 2.1: hydrogen bromide / water / 12 h / 125 °C / Inert atmosphere 3.1: dichloromethane / 1 h / Inert atmosphere 3.2: 48 h / 20 °C / Inert atmosphere View Scheme

Synthesize Find similar

Rx-ID: 33504036 Find similar reactions

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details

150

Synthesize Find similar

Rx-ID: 33504061 Find similar reactions

77%

Stage #1: in dichloromethane

1 h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride in dichloromethane

T=20°C; 48 h; Inert atmosphere;

Synthesize Find similar

Synthesize Find similar

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details

151

Synthesize Find similar

Multi-step reaction with 2 steps

Synthesize Find similar

Rx-ID: 33504232 Find similar reactions

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.


1.1: hydrogen bromide / water / 12 h / 125 °C / Inert atmosphere 2.1: dichloromethane / 1 h / Inert atmosphere 2.2: 48 h / 20 °C / Inert atmosphere View Scheme

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details

152

Synthesize Find similar

Multi-step reaction with 4 steps 1.1: acetic acid / dichloromethane / 0.5 h / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: dichloromethane / 1 h / Inert atmosphere 2.2: 48 h / 20 °C / Inert atmosphere 3.1: hydrogen bromide / water / 12 h / 125 °C / Inert atmosphere 4.1: dichloromethane / 1 h / Inert atmosphere 4.2: 48 h / 20 °C / Inert atmosphere View Scheme

Synthesize Find similar

Rx-ID: 33504236 Find similar reactions

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details

153

Synthesize Find similar

154

Multi-step reaction with 3 steps 1.1: dichloromethane / 1 h / Inert atmosphere 1.2: 48 h / 20 °C / Inert atmosphere 2.1: hydrogen bromide / water / 12 h / 125 °C / Inert atmosphere 3.1: dichloromethane / 1 h / Inert atmosphere 3.2: 48 h / 20 °C / Inert atmosphere View Scheme

Synthesize Find similar

Rx-ID: 33504243 Find similar reactions

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Multi-step reaction with 4 steps 1.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.5 h / -78 °C / Inert atmosphere 1.2: 1.5 h / -78 - 20 °C / Inert atmosphere 2.1: dichloromethane / 1 h / Inert atmosphere 2.2: 48 h / 20 °C / Inert atmosphere 3.1: hydrogen bromide / water / 12 h / 125 °C / Inert atmosphere 4.1: dichloromethane / 1 h / Inert atmosphere 4.2: 48 h / 20 °C / Inert atmosphere View Scheme

Synthesize Find similar

Rx-ID: 33504272 Find similar reactions

Johnson, Mark; Antonio, Tamara; Reith, Maarten E. A.; Dutta, Aloke K.

Journal of Medicinal Chemistry, 2012 , vol. 55, # 12 p. 5826 - 5840 Title/Abstract Full Text View citing articles Show Details

155

Synthesize Find similar

77%

With boron tribromide in dichloromethane

T=20°C; 5 h;

Synthesize Find similar

Rx-ID: 9228343 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

156

Synthesize Find similar

Multi-step reaction with 6 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl / dioxane / 24 h / Heating

Synthesize Find similar

Rx-ID: 14560976 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details


4

5: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 6: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

157

Synthesize Find similar

Multi-step reaction with 4 steps 1: 79 percent / xylene / 96 h / Heating 2: 69 percent / TiCl4 / dioxane / 24 h / Heating 3: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 4: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

Synthesize Find similar

Rx-ID: 14562111 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

158

Synthesize Find similar

Multi-step reaction with 5 steps 1: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 2: 79 percent / xylene / 96 h / Heating 3: 69 percent / TiCl4 / dioxane / 24 h / Heating 4: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 5: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

Synthesize Find similar

Rx-ID: 14562167 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

159

Synthesize Find similar

Synthesize Find similar

Rx-ID: 14567983 Find similar reactions


Multi-step reaction with 6 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl4 / dioxane / 24 h / Heating 5: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 6: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

160

Synthesize Find similar

Multi-step reaction with 2 steps 1: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 2: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

Synthesize Find similar

Rx-ID: 14573664 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

161

Synthesize Find similar

162

Multi-step reaction with 3 steps 1: 69 percent / TiCl4 / dioxane / 24 h / Heating 2: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane 3: 77 percent / BBr3 / CH2Cl2 / 5 h / 20 °C View Scheme

Synthesize Find similar

Rx-ID: 14578298 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Rx-ID: 28548919 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 206 ;

Title/Abstract Full Text Show Details

163

Synthesize Find similar

Rx-ID: 2755098 Find similar reactions

85%

With sodium hydrogencarbonate in tetrahydrofuran; N,Ndimethyl-formamide

5 h; Heating;

Synthesize Find similar

Synthesize Find similar

Malleron, Jean-Luc; Gueremy, Claude; Mignani, Serge; Peyronel, Jean-Francois; Truchon, Alain; et al.

Journal of Medicinal Chemistry, 1993 , vol. 36, # 9 p. 1194 - 1202 Title/Abstract Full Text View citing articles Show Details

164

Synthesize Find similar

Synthesize Find similar

Rx-ID: 31808257 Find similar reactions

Multi-step reaction with 3 steps 1: trichlorophosphate 2: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane 3: lithium perchlorate / acetonitrile / Reflux View Scheme

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

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

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


165

Synthesize Find similar

Multi-step reaction with 2 steps 1: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane 2: lithium perchlorate / acetonitrile / Reflux View Scheme

Synthesize Find similar

Rx-ID: 31808322 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

166

Synthesize Find similar

Rx-ID: 31808325 Find similar reactions

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

Synthesize Find similar

Synthesize Find similar

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

167

Synthesize Find similar

Synthesize Find similar

Rx-ID: 31808543 Find similar reactions

Multi-step reaction with 2 steps 1: lithium perchlorate / acetonitrile / Reflux 2: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane View Scheme

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

Multi-step reaction with 2 steps

Na, Young Min


1.1: lithium perchlorate / acetonitrile / 48 h / Reflux 2.1: acetic acid / ethanol / 1 h / 0 °C 2.2: 12 h / 0 - 40 °C View Scheme

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

168

Synthesize Find similar

Rx-ID: 31808546 Find similar reactions

Synthesize Find similar

With lithium perchlorate in acetonitrile

Reflux;

Synthesize Find similar

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

169

Synthesize Find similar

Rx-ID: 32943556 Find similar reactions

Synthesize Find similar

Stage #1: formaldehyd; (2R,3R)-2-(2,4-difluorophenyl)-3(piperazin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol With acetic acid in ethanol

T=0°C; 1 h; Stage #2: indole in ethanol

T=0 - 40°C; 12 h;

Synthesize Find similar

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

170

Synthesize Find similar

Synthesize Find similar

Rx-ID: 32943580 Find similar reactions

Synthesize Find similar


Multi-step reaction with 7 steps 1.1: dichloromethane / 70 °C 2.1: potassium carbonate / 6 h / 100 °C 3.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 4.1: pyridine / 6 h / 20 °C 5.1: sodium methylate / methanol / 0.5 h / 0 °C 6.1: lithium perchlorate / acetonitrile / 48 h / Reflux 7.1: acetic acid / ethanol / 1 h / 0 °C 7.2: 12 h / 0 - 40 °C View Scheme

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

171

Synthesize Find similar

Multi-step reaction with 4 steps 1.1: pyridine / 6 h / 20 °C 2.1: sodium methylate / methanol / 0.5 h / 0 °C 3.1: lithium perchlorate / acetonitrile / 48 h / Reflux 4.1: acetic acid / ethanol / 1 h / 0 °C 4.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943626 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

172

Synthesize Find similar

173

Multi-step reaction with 3 steps 1.1: sodium methylate / methanol / 0.5 h / 0 °C 2.1: lithium perchlorate / acetonitrile / 48 h / Reflux 3.1: acetic acid / ethanol / 1 h / 0 °C 3.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943650 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 2.1: pyridine / 6 h / 20 °C 3.1: sodium methylate / methanol / 0.5 h / 0 °C 4.1: lithium perchlorate / acetonitrile / 48 h / Reflux 5.1: acetic acid / ethanol / 1 h / 0 °C 5.2: 12 h / 0 - 40 °C View Scheme

Rx-ID: 32943676 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

174

Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 6 steps 1.1: potassium carbonate / 6 h / 100 °C 2.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 3.1: pyridine / 6 h / 20 °C 4.1: sodium methylate / methanol / 0.5 h / 0 °C 5.1: lithium perchlorate / acetonitrile / 48 h / Reflux 6.1: acetic acid / ethanol / 1 h / 0 °C 6.2: 12 h / 0 - 40 °C View Scheme

Rx-ID: 32943701 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

175

Synthesize Find similar

With methanol; sodium cyanoborohydride

T=20°C; 40 h;

Rx-ID: 45192906 Find similar reactions

EXONATE LIMITED; BATES, David; MORRIS, Jonathan; TOOP, Hamish; BATSON, Jennifer

Patent: WO2017/64512 A1, 2017 ;


Location in patent: Page/Page column 34; 55 ;

Hide Experimental Procedure

Title/Abstract Full Text Show Details

General Procedure for the Syntheses of Compound 4

General procedure: Piperazine 3 (1 equiv.) and sodium cyanoborohydride (2 equiv.) were added successively as solids to a 0.1M solution of the R3 aldehyde (R3 as defined elsewhere) (1 equiv.) in methanol. The solution was allowed to stir at room temperature for 40 h. The solvent was removed under reduced pressure. The residue was diluted with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (x3). The organic extracts were combined and washed with brine, then dried (Na2SO4). The solvent was removed under reduced pressure. The crude product was purified by flash chromatography on deactivated silica gel, eluting with 2 - 5 percent methanol/ethyl acetate, to afford the product.

176

Synthesize Find similar

Rx-ID: 25623754 Find similar reactions

SCHERING CORPORATION

Patent: WO2007/11623 A1, 2007 ; Location in patent: Page/Page column 316 ;

Title/Abstract Full Text Show Details

177

Synthesize Find similar

Rx-ID: 9183117 Find similar reactions

79%

Synthesize Find similar

With sodium tris(acetoxy)borohydride in 1,2-dichloro-ethane

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

178

Synthesize

Synthesize Find similar

Synthesize


Find similar

Multi-step reaction with 5 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl4 / dioxane / 24 h / Heating 5: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Find similar

Rx-ID: 14560975 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

179

Synthesize Find similar

Multi-step reaction with 3 steps 1: 79 percent / xylene / 96 h / Heating 2: 69 percent / TiCl4 / dioxane / 24 h / Heating 3: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14562110 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

180

Synthesize Find similar

181

Multi-step reaction with 4 steps 1: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 2: 79 percent / xylene / 96 h / Heating 3: 69 percent / TiCl4 / dioxane / 24 h / Heating 4: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Synthesize Find similar

Rx-ID: 14562166 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 5 steps 1: 74 percent / K2CO3; Cu / various solvent(s) / 4 h / Heating 2: 64 percent / Na2S2O4 / aq. NH3 / 80 °C 3: 79 percent / xylene / 96 h / Heating 4: 69 percent / TiCl4 / dioxane / 24 h / Heating 5: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Rx-ID: 14567982 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

182

Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 2 steps 1: 69 percent / TiCl4 / dioxane / 24 h / Heating 2: 79 percent / NaBH(OAc)3 / 1,2-dichloro-ethane View Scheme

Rx-ID: 14578297 Find similar reactions

Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.

Australian Journal of Chemistry, 2002 , vol. 55, # 9 p. 565 - 576 Title/Abstract Full Text View citing articles Show Details

183

Synthesize Find similar

Rx-ID: 23339493 Find similar reactions

KUDOS PHARMACEUTICALS LIMITED; MAYBRIDGE LIMITED

Patent: WO2004/80976 A1, 2004 ; Location in patent: Page 87 ; Title/Abstract Full Text Show Details


184

Synthesize Find similar

With methanol; sodium cyanoborohydride

T=20°C; 40 h; Hide Experimental Procedure

Rx-ID: 45192870 Find similar reactions

EXONATE LIMITED; BATES, David; MORRIS, Jonathan; TOOP, Hamish; BATSON, Jennifer

Patent: WO2017/64512 A1, 2017 ; Location in patent: Page/Page column 34; 47 ; Title/Abstract Full Text Show Details

General Procedure for the Syntheses of Compound 4

General procedure: Piperazine 3 (1 equiv.) and sodium cyanoborohydride (2 equiv.) were added successively as solids to a 0.1M solution of the R3 aldehyde (R3 as defined elsewhere) (1 equiv.) in methanol. The solution was allowed to stir at room temperature for 40 h. The solvent was removed under reduced pressure. The residue was diluted with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (x3). The organic extracts were combined and washed with brine, then dried (Na2SO4). The solvent was removed under reduced pressure. The crude product was purified by flash chromatography on deactivated silica gel, eluting with 2 - 5 percent methanol/ethyl acetate, to afford the product.

185

Synthesize Find similar

Rx-ID: 28548913 Find similar reactions

ASTRAZENECA AB; ASTRAZENECA UK LIMITED

Patent: WO2009/81197 A1, 2009 ; Location in patent: Page/Page column 204 ;

Title/Abstract Full Text Show Details

186

Synthesize Find similar

Rx-ID: 32943574 Find similar reactions

Synthesize Find similar

Synthesize Find similar

Synthesize Find similar


Stage #1: formaldehyd; (2R,3R)-2-(2,4-difluorophenyl)-3(piperazin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol With acetic acid in ethanol

T=0°C; 1 h; Stage #2: 5-methyl-1H-indole in ethanol

T=0 - 40°C; 12 h;

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

187

Synthesize Find similar

Multi-step reaction with 7 steps 1.1: dichloromethane / 70 °C 2.1: potassium carbonate / 6 h / 100 °C 3.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 4.1: pyridine / 6 h / 20 °C 5.1: sodium methylate / methanol / 0.5 h / 0 °C 6.1: lithium perchlorate / acetonitrile / 48 h / Reflux 7.1: acetic acid / ethanol / 1 h / 0 °C 7.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943586 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

188

Synthesize Find similar

189

Multi-step reaction with 2 steps 1.1: lithium perchlorate / acetonitrile / 48 h / Reflux 2.1: acetic acid / ethanol / 1 h / 0 °C 2.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943608 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Multi-step reaction with 4 steps 1.1: pyridine / 6 h / 20 °C 2.1: sodium methylate / methanol / 0.5 h / 0 °C 3.1: lithium perchlorate / acetonitrile / 48 h / Reflux 4.1: acetic acid / ethanol / 1 h / 0 °C 4.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943632 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

190

Synthesize Find similar

Multi-step reaction with 3 steps 1.1: sodium methylate / methanol / 0.5 h / 0 °C 2.1: lithium perchlorate / acetonitrile / 48 h / Reflux 3.1: acetic acid / ethanol / 1 h / 0 °C 3.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943656 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

191

Synthesize Find similar

192

Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 2.1: pyridine / 6 h / 20 °C 3.1: sodium methylate / methanol / 0.5 h / 0 °C 4.1: lithium perchlorate / acetonitrile / 48 h / Reflux 5.1: acetic acid / ethanol / 1 h / 0 °C 5.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943682 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar

Synthesize Find similar

Multi-step reaction with 6 steps 1.1: potassium carbonate / 6 h / 100 °C 2.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 3.1: pyridine / 6 h / 20 °C 4.1: sodium methylate / methanol / 0.5 h / 0 °C 5.1: lithium perchlorate / acetonitrile / 48 h / Reflux 6.1: acetic acid / ethanol / 1 h / 0 °C 6.2: 12 h / 0 - 40 °C View Scheme

Rx-ID: 32943707 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

193

Synthesize Find similar

Rx-ID: 32943561 Find similar reactions

72%

Synthesize Find similar

Stage #1: formaldehyd; (2R,3R)-2-(2,4-difluorophenyl)-3(piperazin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol With acetic acid in ethanol

T=0°C; 1 h; Stage #2: 5-fluoro-1H-indole in ethanol

T=0 - 40°C; 12 h;

Synthesize Find similar

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

194

Synthesize Find similar

Multi-step reaction with 7 steps 1.1: dichloromethane / 70 °C

Synthesize Find similar

Rx-ID: 32943583 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470

Synthesize Find similar


2.1: potassium carbonate / 6 h / 100 °C 3.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 4.1: pyridine / 6 h / 20 °C 5.1: sodium methylate / methanol / 0.5 h / 0 °C 6.1: lithium perchlorate / acetonitrile / 48 h / Reflux 7.1: acetic acid / ethanol / 1 h / 0 °C 7.2: 12 h / 0 - 40 °C View Scheme

Title/Abstract Full Text View citing articles Show Details

195

Synthesize Find similar

Multi-step reaction with 2 steps 1.1: lithium perchlorate / acetonitrile / 48 h / Reflux 2.1: acetic acid / ethanol / 1 h / 0 °C 2.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943605 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

196

Synthesize Find similar

197

Multi-step reaction with 4 steps 1.1: pyridine / 6 h / 20 °C 2.1: sodium methylate / methanol / 0.5 h / 0 °C 3.1: lithium perchlorate / acetonitrile / 48 h / Reflux 4.1: acetic acid / ethanol / 1 h / 0 °C 4.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943629 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details


Synthesize Find similar Multi-step reaction with 3 steps 1.1: sodium methylate / methanol / 0.5 h / 0 °C 2.1: lithium perchlorate / acetonitrile / 48 h / Reflux 3.1: acetic acid / ethanol / 1 h / 0 °C 3.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943653 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details

198

Synthesize Find similar Multi-step reaction with 5 steps 1.1: toluene-4-sulfonic acid / methanol / 1 h / 20 °C 2.1: pyridine / 6 h / 20 °C 3.1: sodium methylate / methanol / 0.5 h / 0 °C 4.1: lithium perchlorate / acetonitrile / 48 h / Reflux 5.1: acetic acid / ethanol / 1 h / 0 °C 5.2: 12 h / 0 - 40 °C View Scheme

Synthesize Find similar

Rx-ID: 32943679 Find similar reactions

Na, Young Min

Bulletin of the Korean Chemical Society, 2010 , vol. 31, # 11 p. 3467 - 3470 Title/Abstract Full Text View citing articles Show Details


Turn static files into dynamic content formats.

Create a flipbook
Issuu converts static files into: digital portfolios, online yearbooks, online catalogs, digital photo albums and more. Sign up and create your flipbook.