Water → 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

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Reaction Conditions

Reaction Steps

1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation, see Intermediate 7) (18 g, 63.6 mmol) was dissolved in dry NMP (90 mL). 6-chloronicotinonitrile (13.21 g, 95 mmol) and DIPEA (22.20 ml, 127 mmol) were added, the mixture was stirred at 150° C. under a nitrogen atmosphere for 8 h, then allowed to stand overnight at room temperature. The solution was added to water (1 L) and the mixture extracted with EtOAc (2×400 mL). The organic layer was washed with water (2×500 mL), dried and evaporated in vacuo to give a brown foam. This brown foam was purified by silica gel column chromatography (750 g column, eluting with 0-100% EtOAc/cyclohexane). The appropriate fractions were combined and evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (18.7 g, 48.5 mmol, 76% yield) as a pale yellow solid.

Provenance & Evidence