Dimethylformamide → 7-[(1R)-1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-3-(8-methyl-8-azabicyclo[3.2.1]oct-2-en-3-yl)furo[3,2-c]pyridin-6-amine

Participants

Reaction Conditions

Reaction Steps

In a two necked RB flask (50 mL), equipped with a N2 inlet, a water condenser and a magnetic stirrer, were placed 7-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-3-bromofuro[3,2-c]pyridine-6-amine (200 mg, 0.48 mmol), 8-methyl-3-(trimethylstannyl)-8-azabicyclo[3.2.1]oct-2-ene (216 mg, 0.75 mmol), tris(dibenzylideneacetone)dipalladium (100 mg, 0.11 mmol), tri-o-tolylphosphine (26 mg, 0.085 mmol), DMF (10 mL) and triethylamine (1.0 mL). This reaction mixture was heated at 114-116° C. for 4 h. TLC (10% MeOH in DCM) indicated that the starting material was consumed. DMF was removed under reduced pressure; water was added to the residue and extracted with DCM (3×10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was purified on silica gel column chromatography eluting with 2-5% methanol in dichloromethane to give the title compound. 1H NMR (CDCl3, 300 MHz): δ=1.2 (m, 1H), 2.85 (d, J=6.6 Hz, 3H), 2.31 (m, 2H), 2.58 (br, m, 2H), 2.70 (s, 3H), 3.10 (br, d, 1H), 3.90 (d, br, 2H), 4.77 (br, 2H), 6.40 (d, J=6.0 Hz, 1H), 6.55 (m, 1H), 7.01 (t, J=6.6 Hz, 1H), 7.30 (t, J=6.6 Hz, 1H), 7.40 (s, 1H), 8.21 (s, 1H).

Provenance & Evidence