Potassium Carbonate → tert-butyl 5-bromo-2,4-difluoro-6-(1-methyl-1H-indol-5-yl)nicotinate

HRID 1481772Notes

Reaction equation

[Br:1][C:2]1[C:3](Br)=[N:4][C:5]([F:16])=[C:6]([C:14]=1[F:15])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH3:18][N:19]1[C:27]2[C:22](=[CH:23][C:24](B(O)O)=[CH:25][CH:26]=2)[CH:21]=[CH:20]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[Br:1][C:2]1[C:3]([C:24]2[CH:23]=[C:22]3[C:27](=[CH:26][CH:25]=2)[N:19]([CH3:18])[CH:20]=[CH:21]3)=[N:4][C:5]([F:16])=[C:6]([C:14]=1[F:15])[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of tert-butyl 5,6-dibromo-2,4-difluoronicotinate (156 mg, 0.42 mmol), 1-methyl-1H-indol-5-ylboronic acid (80 mg, 0.46 mmol), PdCl2dppf (34 mg, 0.042 mmol), aqueous K2CO3 (2.0 M×0.6 mL, 1.2 mmol) in acetonitrile (1.8 mL) was stirred at 50° C. overnight. The mixture was cooled and extracted with ethyl acetate. The organic layers were combined and dried over sodium sulfate, then evaporated and purified by silica chromatography (0-5% ethyl acetate in hexanes) to give tert-butyl 5-bromo-2,4-difluoro-6-(1-methyl-1H-indol-5-yl)nicotinate (128 mg, 73%).

Workup

temperatureThe mixture was cooled
extractionextracted with ethyl acetate
dry with materialdried over sodium sulfate
customevaporated
custompurified by silica chromatography (0-5% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d1fc0fdfaa6b48c5b8cb293b71291f19
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409905B2

Reaction notes

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