Ethyl Acetate → 1-(5-Cyclopropyl-1H-pyrazol-3-yl)-6-((S)-1-(4-fluorophenyl)ethylamino)-1H-benzo[d]imidazole-4-carbonitrile

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The mixture of (S)-2-amino-3-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-(1-(4-fluorophenyl)ethylamino)benzonitrile (Method 96, 3.95 g, 10 mmol) and formamidine acetate (2.2 g, 21 mmol) in EtOH (50 ml) was heated at reflux for 36 hours. After cooling, the reaction mixture was treated with saturated sodium bicarbonate solution (30 ml) and EtOAc (80 ml). The organic layer was separated, washed with brine (30 ml), and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by column chromatography (EtOAc) to give the title compound as an off-white solid (1.05 g, 26%). 1H NMR (400 MHz) 12.80 (s, 1H), 8.45 (s, 1H), 7.43 (m, 2H), 7.31 (d, J=2.0 Hz, 1H), 7.12 (m, 2H), 7.00 (d, J=2.0 Hz, 1H), 6.75 (d, J=6.8 Hz, 1H), 6.22 (d, J=2.0 Hz, 1H), 4.58 (m, 1H), 1.97 (m, 1H), 1.44 (d, J=6.4 Hz, 3H), 1.03 (m, 2H), 0.75 (m, 2H). MS: Calcd.: 386; Found: [M+H]+ 387.

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