5-Bromo-2-chloropyrimidine → Methyl 1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylate

HRID 630465Notes

Reaction equation

CC([O-])(C)C.[K+].[Br:7][C:8]1[CH:9]=[N:10][C:11](Cl)=[N:12][CH:13]=1.[CH3:15][S:16][C:17]1[C:25]2[C:20](=[CH:21][C:22]([C:26]([O:28][CH3:29])=[O:27])=[CH:23][CH:24]=2)[NH:19][CH:18]=1>CN(C=O)C>[Br:7][C:8]1[CH:9]=[N:10][C:11]([N:19]2[C:20]3[C:25](=[CH:24][CH:23]=[C:22]([C:26]([O:28][CH3:29])=[O:27])[CH:21]=3)[C:17]([S:16][CH3:15])=[CH:18]2)=[N:12][CH:13]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Potassium tert-butylate (4.41 g, 39.36 mmol) and 5-bromo-2-chloro-pyrimidine (5.0 g, 26.2 mmol) were added to a solution of methyl 3-(methylthio)-1H-indole-6-carboxylate (5.8 g, 26.2 mmol) in DMF (60 mL). The resulting mixture was heated at 120° C. for 16 h, then cooled and poured onto ice-cold water (100 mL). The mixture was extracted with MTBE (3×50 mL) and the combined organic layers were dried over sodium sulfate and evaporated. The crude material was purified by column chromatography [100-200 mesh silica; ethyl acetate/hexane=1:9]. White solid. Yield: 6.0 g (61% of theory). HPLC-MS (method 5): Rt=4.15 min; m/z [M+H]+=379

Workup

temperaturecooled
additionpoured onto ice-cold water (100 mL)
extractionThe mixture was extracted with MTBE (3×50 mL)
dry with materialthe combined organic layers were dried over sodium sulfate
customevaporated
customThe crude material was purified by column chromatography [100-200 mesh silica; ethyl acetate/hexane=1:9]

Sources & evidence

ORD record: ord-c8341893b4f244fdb52e28f0aba4469e
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315490B2

Reaction notes

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