[NH2:1][C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].CO[CH:20]1[CH2:24][CH2:23][CH:22](OC)O1>C(O)(=O)C>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([N:1]4[CH:20]=[CH:24][CH:23]=[CH:22]4)[C:3]=3[F:17])[N:6]=2)[CH2:10][CH2:11]16-Amino-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-319) (29 mg, 0.13 mmol) was dissolved in acetic acid (2 ml), then at room temperature, 2,5-dimethoxytetrahydrofuran (49 μl, 0.38 mml) was added. The solution was stirred at 100° C. for 3 hours, then cooled to room temperature. The solvent was evaporated away under reduced pressure, the resulting residue was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, n-hexane:ethyl acetate=9:1, v/v) to obtain the entitled compound (28.5 mg, 81%) as a white solid.
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