1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67398876, compound

Participants

Reaction Steps

2-{[4-(2-Aminoethyl)-1,3-thiazol-2-yl]thio}-2-methylpropionic acid tert-butyl ester (1.51 g) synthesized in Example 7 and 4-cyclohexylbutanoic acid (0.85 g) were dissolved in N,N-dimethylformamide (10 mL), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) hydrochloride (1.05 g) and hydroxybenzotriazole (HOBT) monohydrate (0.85 g) were successively added thereto, and the mixture was stirred at room temperature for 5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1) and the reaction mixture was directly purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=1:1) to give 2-({4-[2-(4-cyclohexylbutanoylamino)ethyl]-1,3-thiazol-2-yl}thio)-2-methylpropionic acid tert-butyl ester (2.2 g) as a colorless oil. The obtained compound (2.2 g) was dissolved in tetrahydrofuran (10 mL), 1 M-borane/tetrahydrofuran complex (19.5 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 12 hr. The reaction mixture was ice-cooled, and methanol (30 mL) was added dropwise. After warming to room temperature, the mixture was stirred for 1 hr. The reaction mixture was concentrated under reduced pressure, piperidine (30 mL) was added, and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; chloroform:methanol=50:1) to give the title compound (1.2 g) as a colorless oil.

Provenance & Evidence