Trifluoroacetic acid → 5-{2-Amino-6-[2-(4-tert-butoxycarbonylaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2-methoxy-4-methylbenzoic acid methyl ester

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Reaction Steps

5-[2-Amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2-methoxy-4-methylbenzoic acid methyl ester (52 mg, 0.11 mmol) obtained in Step 1 above was dissolved with dichloromethane (2.5 ml) in a reaction vessel. Trifluoroacetic acid (0.7 ml) was added to the solution and stirred for 4 hours while gradually warming from 0° C. to room temperature. The reaction solution was concentrated under reduced pressure, and then benzene (1.5 ml) was added to the resulting residue. The solution was concentrated under reduced pressure. This treatment was repeated three times. The obtained pale yellow oily material was dissolved in N,N-dimethylformamide (1.5 ml). 4-tert-Butoxycarbonylaminobutanoic acid (35 mg, 0.17 mmol), N-hydroxybenzotriazole (31 mg, 0.23 mmol), and diisopropylethylamine (0.5 ml, 2.8 mmol) were added to the solution, and then 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (66 mg, 0.34 mmol) was added thereto. The resulting mixture was stirred at room temperature for 2.5 hours. A saturated ammonium chloride solution was added to the reaction solution, and the mixture was extracted with ethyl acetate (100 ml). The ethyl acetate solution was sequentially washed with 1N hydrochloric acid (50 ml), water (50 ml), a saturated aqueous sodium bicarbonate solution (50 ml), water (50 ml), and a saturated aqueous sodium chloride solution (50 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate (10 g). After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate to ethyl acetate:methanol=25:1) to yield 5-{2-amino-6-[2-(4-tert-butoxycarbonylaminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2-methoxy-4-methylbenzoic acid methyl ester (49 mg) as a colorless syrup-like material.

Provenance & Evidence