Reaction Steps
To tert-butyl 7′-methylspiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate (5.0 g, 14.1 mmol) in THF (150 mL) at −78° C. was added dropwise chlorosulfonyl isocyanate (1.5 mL, 16.9 mmol) in THF (50 mL) over a period of 10 minutes. The mixture was stirred at that temperature for 4 hours and then DMF (3.5 mL, 45.9 mmol) was added dropwise and the mixture allowed to stir at room temperature overnight. The mixture was concentrated, diluted with DCM (500 mL) and washed with sat. NaHCO3 (200 mL), brine (200 mL), dried over MgSO4 and evaporated to yield a crude residue that was purified by column chromatography (50-100% dichloromethane/hexane) to give tert-butyl 1′-(methoxysulfonylcarbamoyl)-7′-methyl-spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-carboxylate as a pale yellow oil (1.3 g, 24%). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=8.0 Hz, 1H), 6.98 (d, J=4.0 Hz, 1H), 6.96-6.88 (m, 2H), 6.05 (d, J=4.0 Hz, 1H), 4.09-3.95 (m, 2H), 3.31-3.15 (m, 2H), 2.35 (s, 3H), 2.04 (d, J=14.0 Hz, 2H), 1.92-1.79 (m, 2H), 1.48 (s, 9H). ESI-MS m/z calc. 379.5. found 380.1 (M+1)+; Retention time 2.20 minutes (3 min run), and 7-methylspiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1-carbonitrile (0.5 g, 12%). 1H NMR (400 MHz, DMSO) δ 8.40 (s, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.33 (d, J=4.1 Hz, 1H), 7.17 (s, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.42 (d, J=4.1 Hz, 1H), 3.26-3.09 (m, 4H), 2.33 (s, 3H), 2.19-2.04 (m, 4H). ESI-MS m/z calc. 279.3. found 280.3 (M+1)+; Retention time 1.12 minutes (3 min run).
