Methyl Carbamate → HCID 66549081, compound

Participants

Reaction Steps

A solution of Example 61B (0.35 g, 1.95 mmol), DMF (10 mL), N,N-diisopropyl ethylamine (0.72 mL, 4.1 mmol) and methyl 4-((2,5-dioxopyrrolidin-1-yloxy)carbonylamino)-1H-indazole-1-carboxylate (prepared as in Org. Proc. Res. Dev., 2007, 11, 578; 0.65 g, 1.95 mmol) was stirred at ambient temperature. After 5 minutes, LCMS showed complete conversion to the methyl carbamate intermediate. Methanol (20 mL) and 2N sodium hydroxide (5.86 mmol) were added resulting in a white slurry. The mixture was diluted with water and extracted with ethyl acetate (100 mL). The organic extract was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The mixture was separated using a Chiralpak AD-H column and eluting with 5-50% MeOH:CO2 10 min at 3 mL/min to provide the title compound (303 mg, 31%) and Example 62 (181 mg, 27%). Data for Example 61C: 1H NMR (300 MHz, DMSO-d6) δ 12.98 (bs, 1H), 8.56 (s, 1H), 8.07 (d, J=1.0 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.46-7.36 (m, 1H), 7.32-7.01 (m, 5H), 6.55 (d, J=7.2 Hz, 1H), 4.23-3.99 (m, 3H), 2.16-1.97 (m, 2H), 1.82-1.46 (m, 3H). MS (ESI+) M/Z 339 (M+H)+.

Provenance & Evidence