Methyl iodide → HCID 69060147, compound

Participants

Reaction Steps

To a suspension of sodium hydride (40 mg of 60% dispersion in mineral oil, 1.0 mmol) in 5 mL of THF was added (±)-cis-tert-butyl 4-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate, the intermediate from Example 3 (80 mg, 0.22 mmol) in 3 mL of THF. The mixture was stirred for 30 min and then there was added iodomethane (0.10 mL, 1.6 mmol) and the resulting mixture was allowed to stir at ambient temperature for 18 h. The reaction was filtered through a pad of silica gel and concentrated. The residue was purified by chromatography (ISCO, elution with 1-10% EtOAc in hexane) to afford tert-butyl 5-methyl-4-oxo-6-(trifluoromethyl)-3,3a,4,5-tetrahydro-1H-pyrrolo[3,4-c]quinoline-2(9bH)-carboxylate. To this material in 4 mL of hexane was added HCl (4 mL of a 4N solution in 1,4-dioxane, 16 mmol) and the resulting solution was allowed to stir at ambient temperature overnight. The solvents were removed in vacuo and the residue was purified by HPLC (C18 reverse phase, elution with gradient H2O/CH3CN+0.5% TFA). Pure fractions were combined and concentrated. The residue was partitioned between aq NH4OH and CHCl3, the organics were washed with brine, dried (K2CO3) and concentrated to afford 12 mg (60%) of the title compound of Example 4. 1H NMR (CDCl3): δ 7.60 (d, 1H), 7.42 (d, 1H), 7.18 (t, 1H), 3.81 (dd, 1H), 3.39 (s, 3H), 3.37-30 (m, 2H), 3.22-3.18 (m, 1H), 3.05-2.98 (m, 1H), 2.81 (t, 1H). LRMS (ESI): 271.16 (M+H)+.

Provenance & Evidence