Reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[Cl:16])[NH:12][CH:11]=[CH:10]2.[OH-].[Na+].O.CN([CH:23]=[O:24])C>>[Br:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][C:15]=1[Cl:16])[NH:12][CH:11]=[C:10]2[CH:23]=[O:24]Participants
Procedure
A round-bottom flask was charged with DMF (54 mL). Phosphorus oxychloride (6.21 mL, 66.8 mmol) was added dropwise over 5 minutes, and the reaction mixture was stirred at room temperature for an additional 5 minutes. A solution of 5-bromo-6-chloro-1H-indole (7700 mg, 33.41 mmol) in DMF (7 mL) was added dropwise to the reaction mixture, which caused a precipitate to form. The reaction mixture was then heated to 95° C. for 25 minutes. The reaction mixture was treated with 1N aqueous sodium hydroxide (170 mL) and water (170 mL). The reaction mixture was stirred at 95° C. for 11 minutes. The reaction mixture was cooled to 0° C., and the solids were collected by filtration. The solids were washed with water (50 mL) and diethyl ether (50 mL) and dried in vacuo for 16 hours at 65° C. to afford the title compound (7.77 g, 90%) as a tan solid. MS (AP+) 257.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.40 (s, 1H), 8.38 (s, 1H), 7.80 (s, 1H).
Workup
- customto form
- temperatureThe reaction mixture was then heated to 95° C. for 25 minutes
- stirringThe reaction mixture was stirred at 95° C. for 11 minutes
- temperatureThe reaction mixture was cooled to 0° C.
- filtrationthe solids were collected by filtration
- washThe solids were washed with water (50 mL) and diethyl ether (50 mL)
- customdried in vacuo for 16 hours at 65° C.
Sources & evidence
- ORD record
- ord-f464c0b1052e4b14af58529730b22da5
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08889730B2
Linked notes
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