Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([NH:9]CC(C)(OC2CCCCO2)C)=[CH:4][N:3]=1.Cl.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH:23]1[C:28]([OH:30])=O.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[N:3]1[C:4]2[N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH:23]3[C:28](=[O:30])[NH:9][C:5]=2[CH:6]=[N:7][CH:2]=1
To a mixture of 2,4-dichloro-N-(2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-amine (315 mg, 0.982 mmol) and morpholine-3-carboxylic acid hydrochloride (247 mg, 1.47 mmol) in DMSO (6 ml) was added diisopropylethylamine (0.686 ml, 3.93 mmol), and the reaction mixture was stirred at 95° C. for 4 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. The crude residue was chromatographed by silica gel (hexane/ethyl acetate, 19:1 to 1:1) to afford 2-chloro-5-2-methyl-2-(tetrahydro-2H-pyran-2-yloxy)propyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (96.2 mg, 0.242 mmol, 25% yield) as a pale yellow oil which was used in the next reaction without further purification. MS [M+H] found 397.
読み込み中…
