1,2-Dichloroethane → HCID 69656183, compound

Participants

Reaction Steps

To a stirred solution of N-[5-fluoro-2-(1H-1,2,4-triazol-1-yl)benzyl]-L-prolinamide (86 mg, 0.25 mmol), N-(tert-butoxycarbonyl)-3-cyclopropyl-D-alanine (Example 31, Step C, 57 mg, 0.25 mmol) and HOBt hydrate (33 mg, 0.25 mmol) in DMF (2 mL) was added EDC (48 mg, 0.25 mmol). Diisopropylethylamine was then added in portions (0.1 mL total) to bring the pH of the solution to 6–7 as measured on wetted E. Merck pH indicator strips. The mixture was stirred at ambient temperature for 4 hours. The DMF was removed under reduced pressure and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The EtOAc layer was separated, dried over anhydrous MgSO4, and filtered. The filtrate solvent was removed under reduced pressure and the oily residue was purified by preparative reverse phase HPLC eluting with 95/5 to 5/95 1%TFA H2O/CH3CN in 30 min at a flow rate of 15 mL/min. The product fractions were combined and lyophilized to give 35 mg of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.35 (s, 1H), 8.12 (s, 1H), 7.63 (m, 1H), 7.23–7.29 (m, 1H), 7.02–7.06 (m, 1H), 5.17 (d, J=5.5 Hz, 1H 4.62 (d, J=5.6 Hz, 1H), 4.22–4.41 (m, 4H), 3.94 (br, s, 1H), 3.60 (m, 1H), 2.34 (s, 1H), 1.98 (s, 2H), 1.44 (m, 1H), 1.30 (s, 9H), 0.71–0.73 (m, 1H), 0.47–0.51 (m, 2H), 0.12 (br s, 2H).

Provenance & Evidence