Methyl 4-iodobenzoate → (S)-4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Combine tris(dibenzylideneacetone)dipalladium (0) (16 mg, 0.018 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (14 mg, 0.036 mmol) and sodium t-butoxide (43 mg, 0.452 mmol) in toluene (5 mL) and purge this suspension with nitrogen at room temperature for 5 min. Add (S)-(3,5-bistrifluoromethylbenzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)amine (Example 3, Step 18) (100 mg, 0.181 mmol) followed by methyl-4-iodobenzoate (47 mg, 0.181 mmol) and heat this mixture at 100° C. under nitrogen for 2 h. Cool the mixture to room temperature, dilute with dichloromethane, filter through Celite®, and concentrate under reduced pressure. Chromatograph the residue over silica gel, eluting with hexanes/ethyl acetate (20:1 to 1:2), to provide the title compound as an off-white solid (50 mg, 40%). mp 101-105° C.; TLC Rf 0.50 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.72-1.89 (m, 1H), 2.00-2.32 (m, 3H), 2.29 (s, 3H), 3.33-3.40 (m, 1H), 3.89 (s, 3H), 3.99-4.09 (m, 1H), 4.19 (s, 3H), 4.69-5.33 (m, 3H), 6.68-6.73 (m, 2H), 7.15 (s, 1H), 7.45 (s, 1H), 7.62-7.72 (m, 2H), 7.79 (s, 1H), 7.96-8.05 (m, 2H); ESI MS m/z 687 [C31H27F9N6O2+H]+.

Provenance & Evidence