1-Hydroxybenzotriazole → HCID 25177087, compound

Participants

Reaction Steps

5-{2-Amino-6-[2-(4-aminobutyrylamino)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethylbenzoic acid methyl ester (153 mg, 0.37 mmol) obtained in Step 4 above was dissolved by adding tetrahydrofuran (2 ml), methanol (2 ml), and water (1 ml), and then lithium hydroxide monohydrate (160 mg, 3.82 mmol) was added thereto. The resulting mixture was stirred at room temperature for 8 hours. The reaction solution was cooled to 0° C., and 4N hydrochloric acid-ethyl acetate solution (2 ml) was added thereto. The solvent was distilled off under reduced pressure. The resulting residue was dissolved in dimethylformamide (255 ml). (3-Dimethylaminopropyl)ethylcarbodiimide hydrochloride (736 mg, 3.84 mmol), N-hydroxybenzotriazole (519 mg, 3.84 mmol), and diisopropylethylamine (2.67 ml, 15.32 mmol) were added to the solution, and stirred at room temperature for 14 hours. The reaction solution was distilled off under reduced pressure. Water was added to the resulting residue, and extracted three times with ethyl acetate. The organic layers were combined together and washed with water and a saturated aqueous sodium chloride solution, and then dried over magnesium sulfate. After filtration, anhydrous magnesium sulfate was washed with ethyl acetate. The filtrate and washing solution was combined together, and ethyl acetate was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=20:1) to yield 4-amino-18,20-dimethyl-7-thia-3,5,10,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-11,16-dione (Compound 11) (65 mg, 46%).

Provenance & Evidence