Trifluoroacetic acid → N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-5-ethyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxamide

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Reaction Conditions

Reaction Steps

tert-Butyl[(1R,2R)-2-({[5-ethenyl-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate (103 mg, 0.205 mmol), ammonium formate (128 mg, 2.04 mmol), and 10% Pd/C (109 mg, 0.102 mmol) were dissolved in n-propanol (4.1 mL) and left to stir at 100° C. for 18 h. The solution was cooled to room temperature and filtered through celite. The filtrate was concentrated under reduced pressure and taken up in dichloromethane (2 mL). Trifluoroacetic acid (1 mL, 13.0 mmol) was added to the mixture and stirred for 4 h at room temperature. The solution was then neutralized with aqueous saturated sodium bicarbonate and extracted with dichloromethane (×3). The organic layers were collected and dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by prep HPLC. The compound was neutralized by taking the fractions and adding an aqueous saturated sodium bicarbonate solution and extracting three times with dichloromethane. The combined organics were dried with magnesium sulfate, filtered, and concentrated to afford the title compound as a yellow solid. 1H NMR (500 MHz, CD3SOCD3) δ 8.60 (d, 1H); 8.22 (s, 1H); 8.21 (d, 1H); 7.95 (s, 1H); 7.90 (d, 114, br); 7.29 (dd, 1H); 4.56 (m, 1H); 3.08 (m, 1H); 2.83 (q, 2H); 2.10 (m, 1H); 1.86 (m, 1H); 1.71 (m, 1H); 1.59 (m, 2H); 1.44 (m, 1H); 1.20 (t, 3H). LRMS (APCI) calc'd for (C19H21F2N5OS) [M+H]+, 406.1. found 406.1.

Provenance & Evidence