4-Methylmorpholine → HCID 25177236, compound

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Reaction Steps

(S)-4-Amino-18,20-dimethyl-10,16-dioxo-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-14-carboxylic acid (550 mg, 1.28 mmol) obtained in Example 2-13 was dissolved in a mixture of tetrahydrofuran (13 ml) and methanol (1.5 ml). Isobutylchloroformate (250 μl, 1.92 mmol) and N-methylmorpholine (141 μl, 1.28 mmol) were added to the solution at room temperature. After stirring at room temperature for one hour, the mixture was cooled to 0° C. and an aqueous solution (1.5 ml) of sodium borohydride (97 mg, 2.56 mmol) was added thereto. The mixture was warmed to room temperature, and then diluted with ethyl acetate. The solution was sequentially washed with water and a saturated aqueous sodium chloride solution. The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=10:1) to yield (S)-4-amino-14-hydroxymethyl-18,20-dimethyl-7-thia-3,5,11,15-tetraazatricyclo[15.3.1.12,6]docosa-1(20),2(22),3,5,17(21),18-hexaene-10,16-dione (Compound 68) (205 mg) as a white solid material.

Provenance & Evidence