Dichloromethane → [(R)-1-(4-{[5-tert-butoxycarbonylamino-2-(2-trifluoromethyl-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 (132.7 mg, 0.205 mmol), 4,4,5,5-tetramethyl-2-(2-trifluoromethyl-phenyl)-1,3,2-dioxaborolane (278.3 mg, 1.02 mmol, 5.0 eq.), sodium carbonate (65.0 mg, 0.61 mmol, 3.0 eq.), potassium acetate (60.2 mg, 0.61 mmol, 3.0 eq.), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complexed with dichloromethane (1:1) (33.4 mg, 0.041, mmol, 0.20 eq), ACN (10 mL), and water (2.5 mL). The reaction mixture was degassed with N2 for 10 minutes and then subjected to microwave irradiation at 100° C. for 40 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 50 to 100% ethyl acetate/heptane to give 83.9 mg (57.4%) of desired product as a foam. MS (ESI) m/z: 714.4 [M+H+].

Provenance & Evidence