Trimethylsilyl isocyanate → HCID 10121688, compound

Participants

Reaction Steps

Diisopropylethylamine (0.531 mL, 3.05 mmol), DMAP (5 mg), and trimethylsilyl isocyanate (0.413 mL, 3.05 mmol) were added to a solution of 2-(4-{2-hydroxy-3-[3-(4-iodo-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-benzonitrile in pyridine (3 mL) and CH2Cl2 (6 mL). The reaction mixture was stirred for 20 h, then partitioned between aqueous NaHCO3 and CH2Cl2. The CH2Cl2 layer was washed with brine, dried (Na2SO4), and concentrated. The resulting product was dissolved in CH2Cl2 (5 mL) and treated with 21 wt % sodium ethoxide in EtOH (0.5 mL) for 3 h. The reaction mixture was washed with brine, dried (Na2SO4), and concentrated. Purification by column chromatography (silica, 0-10% MeOH/CH2Cl2) afforded 290 mg (78%) of the title compound. HPLC (reverse phase conditions), tR=4.21 min. MS (electrospray): m/z 612.2 (612.5, calculated for C27H30IN7O2, M++H). 1H NMR (400 MHz, CDCl3): 7.73 (d, J=8.6 Hz, 2H), 7.57 (dd, J=7.6, 1.6 Hz, 1H), 7.50 (t, J=7.8 Hz, 1H), 7.36 (d, J=8.6 Hz, 2H), 7.05 (t, J=7.6 Hz, 1H), 7.00 (d, J=8.4 Hz, 1H), 4.64 (br s, 2H), 4.57 (br s, 2H), 4.30 (br s, 1H), 4.20 (dd, J=14.1, 3.3 Hz, 1H), 4.06 (dd, J=14.1, 6.3 Hz, 1H), 3.82-3.65 (m, 2H), 3.29-3.20 (m, 4H), 3.04-2.80 (m, 6H), 2.68 (br s, 2H).

Provenance & Evidence