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

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Reaction Steps

To a mixture of 4-(imidazo[1,2-b]pyridazin-3-yl)-5-methylthiophene-2-carboxylic acid (0.06 g, 0.24 mmol) and BOP (0.16 g, 0.36 mmol) was added tert-butyl[(1R,2R)-2-amino-3,3-difluorocyclohexyl]carbamate (0.06 g, 0.26 mmol) followed by diisopropylethylamine (0.09 mL, 0.49 mmol). The mixture was allowed stir at room temperature overnight. The resulting solution was diluted with water and extracted three times with dichloromethane. The combined organic layers were dried with magnesium sulfate, filtered, concentrated and to the resulting residue was added dichloromethane and trifluoroacetic acid (1 mL, 53 mmol). The compound was 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 ethyl acetate. 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 8.62 (d, 1H); 8.28 (s, 1H); 8.21 (d, 1H); 7.99 (s, 1H); 7.90 (d, 1H); 7.29 (dd, 1H); 4.55 (m, 1H); 3.08 (m, 1H); 2.47 (s, 3H); 2.11 (m, 1H); 1.85 (m, 1H); 1.71 (m, TH); 1.59 (m, 2H); 1.45 (m, 1H). LRMS (APCI) calc'd for (C18H19F2N5OS) [M+H]+, 392.1. found 392.1.

Provenance & Evidence