Diisopropylethylamine → 9H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate

Participants

Reaction Steps

To 5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxylic acid (26 mg, 0.088 mmol) in DMF (0.4 mL) were added BOP (58 mg, 0.13 mmol) and DIEA (0.062 mL, 0.35 mmol). The mixture was left to stir for 5 min, treated with (1R,6S)-6-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-2,2-difluorocyclohexanaminium chloride (36 mg, 0.088 mmol), and left to stir for 2 h. The mixture was diluted with water and extracted with EtOAc (×3). The combined organics were dried (sodium sulfate), concentrated, and purified by flash chromatography to afford 9H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate. LRMS (APCI) calc'd for (C33H28F4N5O3S) [M+H]+, 650.2. found 650.2.

Provenance & Evidence