Hydrochloric Acid → HCID 71811142, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (+/−)-N-(1-(4-bromophenyl)-2,2,2-trifluoroethyl)-6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-amine (100 mg, 0.2 mmol), ethyl 3-aminopropanoate hydrochloride (90 mg, 0.6 mmol), molybdenum hexacarbonyl (57 mg, 0.21 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (165 mg, 1.07 mmol), palladium(II)acetate (2.4 mg, 0.01 mmol), and tri-tert-butylphosphine tetrafluoroborate (9.4 mg, 0.03 mmol) in acetonitrile (2 mL) was heated to 170° C. for 5 minutes in a microwave. The reaction was diluted with water (20 mL) and extracted with ethyl acetate (2×20 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated. The residue (40 mg) was taken up in tetrahydrofuran (2 mL) and cooled to 0° C. 2 N Aqueous lithium hydroxide (0.4 mL, 0.8 mmol) was added and the mixture was allowed to warm to room temperature and stir for 1 hour. The pH was adjusted to 4 with 1 N aqueous hydrochloric acid. The mixture was extracted with dichloromethane (2×20 mL). The combined organics were washed with water (30 mL) and brine (30 mL), dried over sodium sulfate, filtered, and concentrated. Purification by reversed-phase HPLC gave (+/−)-3-(4-(2,2,2-trifluoro-1-(6-(4-(trifluoromethyl)-1H-imidazol-1-yl)pyridin-3-ylamino)ethyl)benzamido)propanoic acid (12 mg, 31%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.29 (s, 1H), 8.08 (s, 1H), 7.94 (d, J=2.8 Hz, 1H), 7.75 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.0 Hz, 2H), 7.38 (d, J=9.2 Hz, 1H), 7.23 (dd, J=2.8, 8.8 Hz, 1H), 5.40 (m, 1H), 3.51 (t, J=6.8 Hz, 2H), 2.53 (t, J=6.8 Hz, 2H). MS (M+1) 502.0.

Provenance & Evidence