Triethylamine → 7-[(6-Methylpyridin-3-yl)ethynyl]-1,2,3,4,5,6-hexahydro-1,4-methanoazepino[4,3-b]indole

Participants

Reaction Conditions

Reaction Steps

Triethylamine (1.0 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (7.4 mg, 0.014 mmol; Strem), 5-ethynyl-2-methylpyridine (51 mg, 0.43 mmol; International Publication No. WO2005090333), CuI (2.8 mg, 0.014 mmol; Aldrich), magnesium sulfate (2 mg, 0.014 mmol) and the product of Example 30A (80 mg, 0.29 mmol) in anhydrous tetrahydrofuran (1.0 mL). The mixture was purged with a nitrogen stream for 2 minutes, and then it was stirred in a sealed tube under nitrogen at 105° C. for 18 hours. The mixture was cooled to ambient temperature and filtered though a microfiber frit, rinsed with a minimal amount of methanol. The resulting solution was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 60-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4) δ ppm 1.91-1.97 (m, 1H), 2.01-2.12 (m, 1H), 2.56 (s, 3H), 2.85 (dd, J=16.9, 2.3 Hz, 1H), 3.01-3.09 (m, 1H), 3.11-3.20 (m, 2H), 3.46 (t, J=3.7 Hz, 1H), 3.81-3.94 (m, 1H), 6.96-7.02 (m, 1H), 7.21 (dd, J=7.3, 0.9 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.50 (dd, J=7.9, 0.9 Hz, 1H), 7.93 (dd, J=7.9, 2.1 Hz, 1H), 8.67 (d, J=1.8 Hz, 1H); MS (ESI+) m/z 314 (M+H)+.

Provenance & Evidence