1,1'-Carbonyldiimidazole → HCID 118093982, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-[3,4-diamino-2-(2,4-difluorophenoxyl)phenyl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (80.0 mg, 0.156 mmol) in tetrahydrofuran (3.0 mL) was treated with N,N-carbonyldiimidazole (50.0 mg, 0.31 mmol) and stirred at 50° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated and washed with water and brine, dried with magnesium sulfate, filtered, and concentrated in vacuo to give the SEM-protected intermediate which was used without further purification. The crude intermediate was diluted with methylene chloride (4.0 mL) and trifluoroacetic acid (4.0 mL) and stirred at 40° C. for 2 h. The reaction mixture was concentrated, diluted with acetonitrile, adjusted to pH ˜7 with 1 M NaOH, and purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (16 mg, 20%). 1H NMR (500 MHz, DMSO-d6) δ 13.96 (br s, 1H), 11.03 (br s, 1H), 10.91 (br s, 1H), 7.68 (br s, 1H), 7.22-7.05 (m, 3H), 6.97 (d, J=8.0 Hz, 1H), 6.70 (dd, J=8.6, 8.6 Hz, 1H), 6.53-6.39 (m, 1H), 3.46 (s, 3H); LCMS calculated for C20H14F2N5O3 (M+H)+: m/z=410.1. found: 410.1.

Provenance & Evidence