4-Aminobenzonitrile → 4-(5-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine (160 mg, 413 mmol), 4-aminobenzonitrile (53.6 mg, 454 μmol), tris(dibenzylideneacetone)dipalladium(0) (18.9 mg, 20.6 μmol) and DavePhos (17.9 mg, 45.4 mmol) in THF (3 ml) was slightly vacuumed to de-gas, and then lithium bis(trimethylsilyl)amide (1.0 M solution in THF) (1857 μl, 1857 μmol) was added and the microwave tube was sealed under N2 gas. The mixture was heated in a microwave reactor at 100° C. for 30 min. The mixture was poured into DCM (10 ml)-AcOH (0.5 ml) and stirred for 10 min, then Et3N (0.5 ml) was added. Solvent was removed under vacuum and the residue was purified by flash chromatography eluting with MeOH/DCM (1-4%) to give 4-(5-(3-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile. MS Found: (ESI pos. ion) m/z 470 (M+H+).

Provenance & Evidence