2-(Tributylstannyl)pyridine → 4-Amino-6-[(S)-1-(1-cyclopropyl-6-fluoro-7-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamino]-pyrimidine-5-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-amino-6-[(S)-1-(7-bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamino]pyrimidine-5-carbonitrile (70 mg, 0.17 mmol), 2-(tributylstannyl)pyridine (0.06 mL, 0.19 mmol), tetrakis(triphenylphosphine)palladium (19 mg, 10 mol %) and copper(I)-thiophene-2-carboxylate (6 mg, 20 mol %) in dioxane (1 mL) was purged with argon gas then heated at 150° C., for 20 min, in a microwave reactor (Biotage). After cooling to RT, the reaction mixture was diluted with MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc) to afford 442 as a pale yellow solid (17 mg, 24%). LCMS (Method K): RT 3.05 min [M+H]+ 415.07. 1H NMR (DMSO-d6, 400 MHz): δ 8.72 (1H, ddd, J=4.87, 1.81, 0.94 Hz), 8.02 (1H, s), 7.94 (1H, td, J=7.71, 1.84 Hz), 7.73-7.66 (3H, m), 7.45 (1H, ddd, J=7.59, 4.87, 1.16 Hz), 7.30 (2H, s), 7.16 (1H, dd, J=10.65, 8.75 Hz), 5.84-5.75 (1H, m), 3.02-2.95 (1H, m), 1.61 (3H, d, J=6.76 Hz), 1.25-1.20 (1H, m), 0.79-0.69 (1H, m), 0.52-0.43 (1H, m), 0.41-0.28 (1H, m)

Provenance & Evidence