Reaction #66066

Reaction equation

Triethylamine

5-ethynyl-2-methylpyridine

product

7-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

→

title compound

7-[(6-methylpyridin-3-yl)ethynyl]-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe mixture was purged with a nitrogen stream for 2 minutes
2. 2
   TemperatureThe mixture was cooled to ambient temperature
3. 3
   Concentrationconcentrated under vacuum
4. 4
   Filtrationfiltered through a glass microfiber frit
5. 5
   Otherpurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Procedure

Triethylamine (2 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (8.8 mg, 0.017 mmol; Aldrich), 5-ethynyl-2-methylpyridine (60 mg, 0.52 mmol; International Publication No. WO2005090333), CuI (3.3 mg, 0.017 mmol; Aldrich) and the product of Example 1B (100 mg, 0.34 mmol) in anhydrous tetrahydrofuran (2 mL). The mixture was purged with a nitrogen stream for 2 minutes, then stirred under nitrogen at 100° C. for 5 hours in a sealed tube. The mixture was cooled to ambient temperature and concentrated under vacuum. The residue was taken up in dimethyl sulfoxide (5 mL), filtered through a glass microfiber frit and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% 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 (500 MHz, methanol-d4 ) δ ppm 2.05-2.16 (m, 4 H), 2.56 (s, 3 H), 3.02-3.12 (m, 2 H), 3.17-3.21 (m, 1 H), 3.21-3.29 (m, 2 H), 4.24 (s, 2 H), 7.00 (t, J=7.6 Hz, 1 H), 7.24 (dd, J=7.3, 0.9 Hz, 1 H), 7.34 (d, J=7.9 Hz, 1 H), 7.36 (dd, J=7.9, 0.9 Hz, 1 H), 7.94 (dd, J=8.1, 2.3 Hz, 1 H), 8.68 (d, J=1.8 Hz, 1H); MS (APCI) m/z 328 (M+H)+.

Source