1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 86675871, compound

Participants

Reaction Conditions

Reaction Steps

A stirred solution of (S)-1-{(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-3-[3-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionyl}-hexahydro-pyridazine-3-carboxylic acid (R)-1-(3-vinyl-phenyl)-ethyl ester (367 mg, 0.50 mmol) in anhydrous dichloromethane (10 mL) was cooled to 0° C. then treated with trimethylsilyl trimethanesulfonate (135 μL, 2.0 mmol). The reaction mixture was stirred at 0° C. for 1.5 hours, then N,N-diisopropylethylamine (350 μL, 2.0 mmol) was added and the mixture was evaporated. The residue was dissolved in acetonitrile (5 mL) and (R)-3-methoxy-hept-6-enoic acid was added followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (134 mg, 0.70 mmol) and hydroxybenzotriazole (81 mg, 0.50 mmol). The reaction was stirred at room temperature under a nitrogen atmosphere for 16 hours. It was then evaporated to dryness before partitioning between ethyl acetate (20 mL) and water (20 mL). The aqueous was extracted with further ethyl acetate (20 mL), the organic layers were combined, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using ethyl acetate/iso-hexanes 13:7 to give the title compound (123 mg, 32%) as a colourless solid. 1H NMR (300 MHz, CDCl3) δ 0.16 (s, 6H), 0.80-1.00 (m, 17H), 1.34-1.94 (m, 12H), 2.00-2.20 (m, 5H), 2.34-2.53 (m, 3H), 2.63-3.03 (m, 3H), 3.38 (s, 3H), 3.52-3.70 (m, 2H), 4.27-4.38 (m, 2H), 4.92-5.10 (m, 2H), 5.29 (d, J=10.9 Hz, 1H), 5.64-5.98 (m, 2H), 6.52-6.99 (m, 4H), 7.22-7.42 (m, 2H). LCMS (m/z) 777.0 [M+H] Tr=5.96 min.

Provenance & Evidence