[(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 → (R)-5-amino-N-(5-(4-aminoazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-(trifluoromethyl)phenyl)thiazole-4-carboxamide

Participants

Reaction Conditions

Reaction Steps

A heterogeneous mixture of [(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 (83.9 mg, 0.117 mmol) in 1,4-dioxane (1.0 mL) and 2M aq. HCl (10 mL) was stirred at 120° C. under N2 for 16 h. The resultant homogeneous reaction was then slowly quenched with saturated aq. NaHCO3 solution and then extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified via reverse phase HPLC to afford 210 (33.4 mg, 59.2%) as a white solid. 1H NMR (400 MHz, DMSO) δ 8.51 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.78 (d, J=4.1 Hz, 2H), 7.68 (dd, J=8.1 Hz, 3.9 Hz, 1H), 7.58 (s, 1H), 7.46 (broad s, 2H), 3.64 (s, 3H), 3.10 (t, J=5.3 Hz, 4H), 3.02-2.90 (m, 1H), 1.89-1.73 (m, 3H), 1.64-1.44 (m, 3H); 2 protons buried in water peak; MS (ESI) m/z: 480.1 [M+H]+

Provenance & Evidence