Dichloromethane → HCID 71256179, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of (E)-N-(4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide (32) (174 mg, 0.36 mmol), 4-chlorophenylboronic acid (68 mg. 0.44 mmol) and K3PO4.3H2O (292 mg, 1.1 mmol) in DME (3 mL) and water (0.5 mL) was added Pd(dppf)Cl2.DCM (15 mg, 0.02 mmol). The resulting mixture was purged with N2 (3×) before heated to 80° C. overnight under N2 atmosphere. The mixture was cooled down to room temperature. The solvents were evaporated and the residue was pre-purified by column chromatography (silica gel, methanol in methylene chloride (1% Et3N)) followed by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% NH3)) to give (E)-N-(4-(4-amino-3-(4-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(dimethylamino)-N-methylbut-2-enamide (33) (41 mg, yield 25%) as a white solid. LC-MS (ESI): m/z (M/M+2) 463/465. 1H NMR (400 MHz, DMSO) δ 8.38 (s, 1H), 8.29 (d, J=8.8 Hz, 2H), 7.77 (d, J=8.4 Hz, 2H), 7.63 (d, J=8.5 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 6.69-6.60 (m, 1H), 5.94 (s, 1H), 3.27 (s, 2H), 2.88 (d, J=5.8 Hz, 1H), 2.03 (s, 3H).

Provenance & Evidence