Toluene → 7-Benzyl-N-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine

Participants

Reaction Conditions

Reaction Steps

The 2-Benzyl-5-bromo-1,2,3,4-tetrahydro-2,6-naphthyridine (see WO03/076427) (250 mg, 0.82 mmol) was dissolved in 1 mL of anhydrous toluene. To the mixture was added Pd2(dba)3 (10 mol %, 85 mg) and PdCl2(DPPF) (33 mg, 5 mol %), followed by NaOtBu (118 mg, 1.23 mmol). After mixing for 5 min, 4-(trifluoromethyl)aniline (0.153 mL, 1.23 mmol) was added and the mixture was heated at 160° C. for 1200 s in a Personal Chemistry microwave. The reaction mixture was filtered and the solvent was evaporated and the residue was dissolved in ethyl acetate and washed with sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a brown-purple residue. The residue was purified using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as an off-white powder (288 mg, 92%).

Provenance & Evidence