Lithium Hexamethyldisilazide → 4-(8-(3-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(4-methoxybenzyl)-4-(2-fluoropyridin-3-yl)-1H-pyrazolo[3,4-d]pyrimidine (150 mg, 447 mmol) and 4-(8-amino-7-methylquinazolin-4-ylamino)benzonitrile (135 mg, 492 mmol) in THF (3 ml) was sonicated until the solid became a fine powder. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0 M solution in THF) (1476 μl, 1476 mmol) slowly. The mixture was stirred at it for 4 hr (LCMS: some SM) and then heated in a microwave synthesizer at 60° C. for 20 min The mixture was poured into MeOH (15 ml) and AcOH (0.5 ml) was added and then NH3/MeOH (2 M, 20 mL) was added. Solvent was removed in vacuo. The product was purified by flash chromatography eluting with MeOH/DCM (1-5%) to give 4-(8-(3-(1-(4-methoxybenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-ylamino)-7-methylquinazolin-4-ylamino)benzonitrile. MS Found (ESI pos. ion) m/z 591 (M+H+).

Provenance & Evidence