[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[C:3]=1[NH:9][CH2:10][CH2:11][CH2:12][OH:13].[N:14]([C:17]1[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=1)=[C:15]=S.Cl.CN(C)CCCN=C=NCC.CN(C)C>O1CCCC1.C(OCC)(=O)C.O>[NH2:8][C:4]1[C:3]2[N:9]([CH2:10][CH2:11][CH2:12][OH:13])[C:15]([NH:14][C:17]3[C:18]([O:25][CH3:26])=[N:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)=[N:1][C:2]=2[CH:7]=[CH:6][CH:5]=1
To a solution of 3-[(2,6-diaminophenyl)amino]propan-1-ol (Reference Example 115; 363 mg, 2.00 mmol) in tetrahydrofuran (5.0 mL) was added 5-isothiocyanato-2,4-dimethoxypyrimidine (440 mg, 2.20 mmol) portionwise at room temperature. After stirring for 2 hr, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (422 mg, 2.20 mmol) and trimethylamine (0.331 mL, 2.40 mmol) was added. The mixture was warmed to 50° C. and stirred for additional 3 hr. Water and ethyl acetate were added to the mixture and the insoluble materials were filtered off. The filtrate was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 0-15% methanol/ethyl acetate gradient mixture. The filtrate was concentrated in vacuo to give the title compound (99 mg, 0.287 mmol, 14%) as a pale yellow amorphous.
Loading…
