Methyl Carbamate → 1-(1H-indazol-4-yl)-3-[(1S,4R)-4-phenylcyclopent-2-en-1-yl]urea

Participants

Reaction Steps

A solution of Example 48C (455 mg, 2.86 mmol), DMF (8 mL), diisopropylethylamine (1.05 mL, 6.01 mmol), and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (prepared as in Org. Proc. Res. Dev., 2007, 950 mg, 2.86 mmol) was stirred at room temperature. After 15 minutes, LCMS showed complete conversion to methyl carbamate. Methanol (16 mL) and 50% aqueous sodium hydroxide (0.50 mL, 8.6 mmol) were added to the reaction mixture. After 10 minutes, LCMS showed complete conversion to product. Water (24 mL) was added dropwise, and the resulting white slurry was stirred at room temperature for 15 minutes. The slurry was filtered and washed with 1:1 MeOH/water (10 mL). The white solid was dried in a vacuum oven at 50° C. to provide the title compound (646 mg, 2.03 mmol, 71% over three steps). 1H NMR (300 MHz, DMSO-d6) δ 13.11-12.64 (m, 1H), 8.56 (s, 1H), 8.06 (d, J=0.9 Hz, 1H), 7.63 (d, J=7.4 Hz, 1H), 7.52-7.30 (m, 2H), 7.21 (m, 4H), 7.05 (d, J=8.3 Hz, 1H), 6.59 (d, J=8.1 Hz, 1H), 5.93 (s, 2H), 4.86 (q, J=7.8 Hz, 1H), 3.86 (t, J=7.3 Hz, 1H), 2.90 (dt, J=13.1, 8.2 Hz, 1H), 1.47-1.28 (m, 1H); MS (DCI) m/z 319 (M+H)+.

Provenance & Evidence