Reactions (25)
Yield
Substances (28)
Citations (9)
Conditions
References
1
Synthesize Find similar Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 16 h / 20 °C 2: N-bromosuccinmide / tert-butyl alcohol / 2 h / 20 °C View Scheme
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Rx-ID: 33407139
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Kawakita, Youichi; Banno, Hiroshi; Ohashi, Tomohiro; Tamura, Toshiya; Yusa, Tadashi; Nakayama, Akiko; Miki, Hiroshi; Iwata, Hidehisa; Kamiguchi, Hidenori; Tanaka, Toshimasa; Habuka, Noriyuki; Sogabe, Satoshi; Ohta, Yoshikazu; Ishikawa, Tomoyasu
Journal of Medicinal Chemistry, 2012 , vol. 55, # 8 p. 3975 - 3991 Title/Abstract Full Text View citing articles Show Details
2
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Rx-ID: 33407211
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With N-bromosuccinmide in tert-butyl alcohol
T=20°C; 2 h;
Kawakita, Youichi; Banno, Hiroshi; Ohashi, Tomohiro; Tamura, Toshiya; Yusa, Tadashi; Nakayama, Akiko; Miki, Hiroshi; Iwata, Hidehisa; Kamiguchi, Hidenori; Tanaka, Toshimasa; Habuka, Noriyuki; Sogabe, Satoshi; Ohta, Yoshikazu; Ishikawa, Tomoyasu
Journal of Medicinal Chemistry, 2012 , vol. 55, # 8 p. 3975 - 3991 Title/Abstract Full Text View citing articles Show Details
3
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Rx-ID: 33407370
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Kawakita, Youichi; Banno, Hiroshi; Ohashi, Tomohiro; Tamura, Toshiya; Yusa, Tadashi; Nakayama, Akiko; Miki, Hiroshi; Iwata, Hidehisa; Kamiguchi, Hidenori; Tanaka, Toshimasa; Habuka, Noriyuki; Sogabe, Satoshi; Ohta, Yoshikazu; Ishikawa, Tomoyasu
Journal of Medicinal Chemistry, 2012 , vol. 55, # 8 p. 3975 - 3991 Title/Abstract Full Text View citing articles Show Details
4
Synthesize Find similar Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide / 0.5 h / 0 °C 1.2: 2 h / 20 °C 2.1: bromine / dichloromethane / 0.25 h / 0 °C View Scheme
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Rx-ID: 31403713
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Tanaka, Minoru; Hikawa, Hidemasa; Yokoyama, Yuusaku
Tetrahedron, 2011 , vol. 67, # 33 p. 5897 - 5901 Title/Abstract Full Text View citing articles Show Details
5
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Rx-ID: 31403733
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With bromine in dichloromethane
T=0°C; 0.25 h; Hide Experimental Procedure
Tanaka, Minoru; Hikawa, Hidemasa; Yokoyama, Yuusaku
Tetrahedron, 2011 , vol. 67, # 33 p. 5897 - 5901 Title/Abstract Full Text View citing articles Show Details
4.2. General procedure for the synthesis of substituted 3-bromoindole derivatives
General procedure: Sodium hydride (132 mg, 3.3 mmol) was added to a stirred solution of the indole (3 mmol) in DMF (6.0 mL) at 0 °C, then stirred for 30 min. To the reaction mixture, tosyl chloride (629 mg, 3.3 mmol) was added and stirred at room temperature for 2 h. After pouring into water, the mixture was extracted with ethyl acetate (2.x.50 mL). The combined organic layers were washed with brine (2.x.50 mL), dried over sodium sulfate, and concentrated in vacuo. The residue was solved in dichloromethane (30 mL) and cooled on iced bath. To the reaction mixture, bromine (170 μL, 3.3 mmol) was added and stirred at 0 °C for 15 min. The reaction mixture was concentrated in vacuo, the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the product.
6
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Rx-ID: 31403740
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Tanaka, Minoru; Hikawa, Hidemasa; Yokoyama, Yuusaku
Tetrahedron, 2011 , vol. 67, # 33 p. 5897 - 5901 Title/Abstract Full Text View citing articles Show Details
7
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With N-bromosuccinmide in tetrahydrofuran; hexane
T=-78°C; 3 h;
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Rx-ID: 8714426
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Amat; Seffar; Llor; Bosch
Synthesis, 2001 , # 2 p. 267 - 275 Title/Abstract Full Text View citing articles Show Details
8
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Rx-ID: 15541183
Find similar Multi-step reaction with 2 steps 1.1: BuLi / tetrahydrofuran; hexane / 0.25 h / -10 °C 1.2: tetrahydrofuran; hexane / 3 h / 0 °C 2.1: 6.8 g / NBS / tetrahydrofuran; hexane / 3 h / -78 °C View Scheme
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Amat; Seffar; Llor; Bosch
Synthesis, 2001 , # 2 p. 267 - 275 Title/Abstract Full Text View citing articles Show Details
9
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Rx-ID: 15543559
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Amat; Seffar; Llor; Bosch
Synthesis, 2001 , # 2 p. 267 - 275 Title/Abstract Full Text View citing articles Show Details
10
Synthesize Find similar Multi-step reaction with 2 steps 1.1: potassium carbonate / acetone / 6 h / Inert atmosphere; Reflux 2.1: n-butyllithium / tetrahydrofuran / -79 - -10 °C / Inert atmosphere 2.2: -78 °C / Inert atmosphere View Scheme
11
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Rx-ID: 31702242
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Lebar, Matthew D.; Hahn, Kristopher N.; Mutka, Tina; Maignan, Patrick; McClintock, James B.; Amsler, Charles D.; Van Olphen, Alberto; Kyle, Dennis E.; Baker, Bill J.
Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 19 p. 5756 - 5762 Title/Abstract Full Text View citing articles Show Details
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Rx-ID: 31702245
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85%
Stage #1: With n-butyllithium in tetrahydrofuran
T=-79 - -10°C; Inert atmosphere; Stage #2: With N-bromosuccinmide in tetrahydrofuran
T=-78°C; Inert atmosphere;
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Lebar, Matthew D.; Hahn, Kristopher N.; Mutka, Tina; Maignan, Patrick; McClintock, James B.; Amsler, Charles D.; Van Olphen, Alberto; Kyle, Dennis E.; Baker, Bill J.
Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 19 p. 5756 - 5762 Title/Abstract Full Text View citing articles Show Details
12
Synthesize Find similar With N-bromosuccinmide in tetrahydrofuran
T=-78°C; Bromination; 4 h;
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Rx-ID: 5347333
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Gerasimov, Madina; Marona-Lewicka, Danuta; Kurrasch-Orbaugh, Deborah M.; Qandil, Amjad M.; Nichols, David E.
Journal of Medicinal Chemistry, 1999 , vol. 42, # 20 p. 4257 - 4263 Title/Abstract Full Text View citing articles Show Details
13
Synthesize Find similar Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 1 h / 0 - 20 °C 1.2: tetrahydrofuran / 2.5 h / 0 °C 2.1: N-bromosuccinimide / tetrahydrofuran / 4 h / -78 °C View Scheme
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Rx-ID: 15955183
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Gerasimov, Madina; Marona-Lewicka, Danuta; Kurrasch-Orbaugh, Deborah M.; Qandil, Amjad M.; Nichols, David E.
Journal of Medicinal Chemistry, 1999 , vol. 42, # 20 p. 4257 - 4263 Title/Abstract Full Text View citing articles Show Details
14
Synthesize Find similar Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 1 h / 0 - 20 °C 1.2: tetrahydrofuran / 2.5 h / 0 °C 2.1: N-bromosuccinimide / tetrahydrofuran / 4 h / -78 °C View Scheme
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Rx-ID: 15964720
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Gerasimov, Madina; Marona-Lewicka, Danuta; Kurrasch-Orbaugh, Deborah M.; Qandil, Amjad M.; Nichols, David E.
Journal of Medicinal Chemistry, 1999 , vol. 42, # 20 p. 4257 - 4263 Title/Abstract Full Text View citing articles Show Details
A
B
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15
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Rx-ID: 43186123
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A: 30% B: 25%
With tetrabutylammomium bromide; caesium carbonate in N,N-dimethyl-formamide
T=0 - 20°C; 48 h; Hide Experimental Procedure
PHARMAKEA, INC.; ROWBOTTOM, Martin W.; HUTCHINSON, John Howard; LONERGAN, David
Patent: WO2016/144702 A1, 2016 ; Location in patent: Paragraph 00383 ; Title/Abstract Full Text Show Details
22.1:Step 1: 2-((1-(4-fluorophenethyl)-1H-indol-4-yl)oxy)isonicotinonitrile (3) and 2-((3-bromo- 1-(4-fluorophenethyl)-1H-indol-4-yl)oxy)isonicotinonitrile (4)
To a stirred solution of 2-((1H-indol-4-yl) oxy) isonicotinonitrile 1 (150 mg, 0.64 mmol) (from Example 47, Step 1) in DMF (5 mL) at 0 °C, were added 1-(2-bromoethyl)-4- fluorobenzene 2 (194 mg, 0.96 mmol), Cs2CO3 (416 mg, 1.28 mmol) and nBu4NBr (10 mg, 0.03 mmol). The mixture was warmed to RT and stirred for 48 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2 x 30 mL). The combined organic extracts were washed with brine (15 mL), dried (Na2504), filtered, and concentrated under reduced pressure. The residue was purified via preparative HPLC to afford compound 3 (70 mg, 30percent) and compound 4 (70 mg, 25percent) both as a pale yellow oil.j00384j Analytical data for Compound 3: ‘HNMR(400IVIHz, CDC13): 8.34 (dd, J 5.1, 0.7 Hz, 1H), 7.24-7.22 (m, 2H), 7.18 (dd, J= 5.1, 1.3 Hz, 1H), 7.09-7.07 (m, 1H), 7.03-6.88 (m, 5H), 6.84 (d, J= 3.2 Hz, 1H), 6.16 (d, J= 3.1 Hz, 1H), 4.34 (t, J= 7.2 Hz, 2H), 3.10 (t, J 7.2 Hz, 2H); LCMS Mass: 358.0 (M+1). A
B
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16
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Find similar Rx-ID: 43186166
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Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 150 °C / |Microwave irradiation 2: tetrabutylammomium bromide; caesium carbonate / N,N-dimethyl-formamide / 48 h / 0 20 °C View Scheme
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PHARMAKEA, INC.; ROWBOTTOM, Martin W.; HUTCHINSON, John Howard; LONERGAN, David
Patent: WO2016/144702 A1, 2016 ; Title/Abstract Full Text Show Details
A
B
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17
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Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h / 150 °C / |Microwave irradiation 2: tetrabutylammomium bromide; caesium carbonate / N,N-dimethyl-formamide / 48 h / 0 20 °C View Scheme
PHARMAKEA, INC.; ROWBOTTOM, Martin W.; HUTCHINSON, John Howard; LONERGAN, David
Patent: WO2016/144702 A1, 2016 ; Title/Abstract Full Text Show Details
18
Synthesize Find similar 90%
19
With N-bromosuccinmide in tetrahydrofuran
T=-78°C; Bromination; 2 h;
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Rx-ID: 8591449
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Vedejs, Edwin; Barda, David A.
Organic Letters, 2000 , vol. 2, # 8 p. 1033 - 1035 Title/Abstract Full Text View citing articles Show Details
Synthesize Find similar Multi-step reaction with 2 steps 1: 100 percent / n-BuLi / hexane; tetrahydrofuran / 2 h / -78 °C 2: 90 percent / N-bromosuccinimide / tetrahydrofuran / 2 h / -78 °C View Scheme
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Rx-ID: 15913757
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Vedejs, Edwin; Barda, David A.
Organic Letters, 2000 , vol. 2, # 8 p. 1033 - 1035 Title/Abstract Full Text View citing articles Show Details
20
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Rx-ID: 15914198
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Vedejs, Edwin; Barda, David A.
Organic Letters, 2000 , vol. 2, # 8 p. 1033 - 1035 Title/Abstract Full Text View citing articles Show Details
21
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Rx-ID: 25604724
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Roche Palo Alto LLC
Patent: US2007/15744 A1, 2007 ; Location in patent: Page/Page column 59-60 ; Title/Abstract Full Text Show Details
22
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Stage #1: With sodium tetrahydroborate; cobalt(II) chloride in tetrahydrofuran; methanol
T=20°C; 3 h; Stage #2: With hydrogenchloride in diethyl ether
T=0°C; 0.5 h; Hide Experimental Procedure
Rx-ID: 43186032
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PHARMAKEA, INC.; ROWBOTTOM, Martin W.; HUTCHINSON, John Howard; LONERGAN, David
Patent: WO2016/144702 A1, 2016 ; Location in patent: Paragraph 00376-00378; 00386 ; Title/Abstract Full Text Show Details
55:Step 2: (2-((1-(6-methoxypyridin-3-yl)-1H-indol-4-yl)oxy)pyridin-4-yl)methanamine hydrochloride (Compound 2-20)
General procedure: To a stirred solution of compound 2 (130 mg, 0.38 mmol) in THF/MeOH (1:1, 8 mL) at 0 °C were added CoCl2 (98 mg, 0.76 mmol) and NaBH4 (144 mg, 3.8 mmol) portion wise. The mixture was warmed to RT and stirred for 3 h. The reaction mixture was filtered through a pad of celite and the residue was washed with 10percent MeOH in CH2C12 (20 mL). The filtrate was washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified via trituration with CH2C12/ n-pentane (2 x 5 mL) to afford the desired amine. To this amine in CH2C12 (2 mL) was added 2M HC1 in Et20 (3 mL) at 0 °C and stirred for 30 mm. The mixture was concentrated under reduced pressure and the obtained solid triturated with Et20/n-pentane (2 x 5 mL) to afford compound 2-20 as a pale green solid (80 mg, 49percent). ‘HNMR (400 MHz, DMSO-d6): 8.68 (br s, 2H), 8.42 (d, J= 2.3 Hz, 3H), 8.14 (d, J= 5.1 Hz, 1H), 7.98 (dd, J= 8.8, 2.8 Hz, 1H), 7.55 (d, J= 3.2 Hz, 1H), 7.3 1-7.25 (m, 3H), 7.23-7.18 (m, 1H), 7.05 (d, J 8.9 Hz, 1H), 6.88 (dd, J= 7.6, 0.7 Hz, 1H), 6.32 (dd, J= 3.3, 0.7 Hz, 1H), 4.11 (q,J= 5.8 Hz, 2H), 3.94 (s, 3H); LCMS Mass: 347.1 (M+1).
23
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24
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.17 h / -78 - -10 °C / Inert atmosphere 1.2: -78 - 0 °C / Inert atmosphere 2.1: N-bromosuccinmide / tetrahydrofuran; hexane / 2 h / -78 °C / Inert atmosphere View Scheme
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Rx-ID: 31235957
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Lebar, Matthew D.; Baker, Bill J.
Australian Journal of Chemistry, 2010 , vol. 63, # 6 p. 862 - 866 Title/Abstract Full Text View citing articles Show Details
Synthesize Find similar Multi-step reaction with 3 steps 1.1: 1H-imidazole / N,N-dimethyl-formamide / 1 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.17 h / -78 - -10 °C / Inert atmosphere 2.2: -78 - 0 °C / Inert atmosphere 3.1: N-bromosuccinmide / tetrahydrofuran; hexane / 2 h / -78 °C / Inert atmosphere View Scheme
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Rx-ID: 31235962
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Lebar, Matthew D.; Baker, Bill J.
Australian Journal of Chemistry, 2010 , vol. 63, # 6 p. 862 - 866 Title/Abstract Full Text View citing articles Show Details
25
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With N-bromosuccinmide in tetrahydrofuran; hexane
T=-78°C; 2 h; Inert atmosphere;
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Rx-ID: 31235966
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Lebar, Matthew D.; Baker, Bill J.
Australian Journal of Chemistry, 2010 , vol. 63, # 6 p. 862 - 866 Title/Abstract Full Text View citing articles Show Details