Dichloromethane → [(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2,4-difluoro-phenyl)-thiazole-4-carbonyl]-amino}-2-methyl-2H-pyrazol-3-yl)-perhydro-azepin-4-yl]-carbamic acid benzyl ester

Participants

Reaction Steps

In a microwave vial was placed ((R)-1-{4-[(2-bromo-5-tert-butoxycarbonylamino-thiazole-4-carbonyl)-amino]-2-methyl-2H-pyrazol-3-yl}-perhydro-azepin-4-yl)-carbamic acid benzyl ester (78.2 mg, 0.12 mmol), 2-(2,4-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (101.3 mg, 0.42 mmol, 3.5 eq.), cesium carbonate (196.4 mg, 0.60 mmol, 5.0 eq), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complexed with dichloromethane (1:1) (29.5 mg, 0.036 mmol, 0.30 eq), and anhydrous N,N-dimethylformamide (3.5 mL). The reaction mixture was degassed with N2 for 10 minutes and then subjected to microwave irradiation at 100° C. for 30 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and then filtered through a pad of Celite. The filtrate was washed with 50% brine/water, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified via flash column chromatography eluted with 40 to 100% ethyl acetate/heptane to give 46.4 mg (56.5%) of desired product as a white solid. 1H NMR (400 MHz, CDCl3) δ 10.35 (s, 1H), 8.63 (s, 1H), 8.14-8.04 (m, 1H), 7.82 (s, 1H), 7.31 (s, 5H), 7.03-6.87 (m, 2H), 5.11-5.00 (s, 2H), 4.84-4.74 (m, 1H), 3.95-3.85 (m, 1H), 3.74 (s, 3H), 3.35-3.24 (m, 2H), 3.23-3.11 (m, 2H), 2.18-2.03 (m, 2H), 1.97-1.65 (m, 4H), 1.53 (s, 9H); MS (ESI) m/z: 682.6 [M+H]+.

Provenance & Evidence