Triethylamine → HCID 67228791, compound

Participants

Reaction Steps

To a solution of the (1S,3R)-1-isopropyl-3-(2,2,2-trifluoro-N-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-yl)acetamido)cyclopentanecarboxylic acid (0.95 g, 2.5 mmol) in CH2Cl2 (5 mL) under N2 at 0° C. is added oxalyl chloride (623 mg, 4.98 mmol) and DMF (3 drops). The mixture is allowed to warm to RT and stir for 2 hr, It was then concentrated. The acid chloride was redissolved in DCM (10 ml), cooled to 0° C., and treated with (1R,4R,7S)-tert-butyl 7-hydroxy-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylate (534 mg, 0.249 mmol), followed by Et3N (0.1 ml, 0.75 mmol). The resulting mixture was warmed to RT and stirred for 2 hrs. The solution was then washed with NaHCO3 (1×5 ml), and brine (1×5 ml). The organic layer was then dried over MgSO4, filtered and concentrated, purified by chromatography (100% EtOAc-60% MeOH/EtOAc) to yield crude intermediate which was dried and concentrated. Then it was dissolved in EtOH (2 ml) and treated with NaOH (3 ml, 7.5 mmol) overnight. The reaction mixture was then purified by chromatography (100% EtOAc-100% MeOH) to yield desired product (300 mg, 25%). LC/MS (M+H)=482.3230 exp, 482.3334 obs; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.67 (dd, J=6.95, 3.66 Hz, 3H) 0.80 (dd, J=6.59, 2.93 Hz, 3H) 1.22 (br. s., 1H) 1.35-1.41 (m, 12H) 1.43-1.48 (m, 2H) 1.55-1.68 (m, 2H) 1.85-1.93 (m, 1H) 1.95-2.04 (m, 1H) 2.16-2.28 (m, 1H) 2.66-2.80 (m, 1H) 2.97-3.02 (m, 1H) 3.03-3.10 (m, 2H) 3.17-3.29 (m, 5H) 3.37-3.47 (m, 1H) 3.47-3.58 (m, 1H) 3.61-3.74 (m, 1H) 3.81-3.89 (m, 1H) 3.94-4.04 (m, 2H) 4.24 (br. s., 1H) 5.65-5.77 (m, 1H)

Provenance & Evidence