Acetone Cyanohydrin → HCID 46938169, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (2S)-2-(1-(2-bromo-6-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-methylpyrazin-2-yl)-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanamide (Intermediate BO1) (1 equiv) in inerted* DMF (5 rel vols) and diisopropylethylamine (DIPEA) (1.25 equivs) was kept in an inert atmosphere and was added with stirring to an inerted* mixture of tris(dibenzylideneacetone)dipalladium(0) (0.025 equivs), sodium acetate (0.1 equiv) and 1,1′-bis(diphenylphosphino)ferrocene (0.075 equivs) in DMF (5 rel vols) at 90° C. over 5 minutes. The mixture was stirred for 10 minutes and then an inerted* solution of acetone cyanohydrin (1.4 equivs) in DMF (2 rel vols) was added over 20 hours with stirring. When the reaction was completed the mixture was cooled to 5° C. and diluted with methyl tert-butyl ether (7 rel vols) and then sodium bicarbonate (0.3 equivs) in water (2.5 rel vols). The organic phase was separated and the aqueous phase washed with methyl tert-butyl ether. The combined organic extract and organic washings were evaporated under reduced pressure at 35° C. and the residue was purified by chromatography. Yield 74%. *Nitrogen bubbled through before use.

Provenance & Evidence