[H-].[Li+].[NH2:3][C:4]1[N:12]=[C:11]2[C:7]([NH:8][CH:9]=[N:10]2)=[C:6]([O:13][CH2:14][CH2:15][O:16][CH3:17])[N:5]=1.[CH2:18]([O:20][P:21]([CH2:26][O:27][CH2:28][CH2:29][CH2:30]Br)([O:23][CH2:24][CH3:25])=[O:22])[CH3:19].O>CN(C)C=O>[NH2:3][C:4]1[N:12]=[C:11]2[C:7]([N:8]=[CH:9][N:10]2[CH2:30][CH2:29][CH2:28][O:27][CH2:26][P:21]([O:23][CH2:24][CH3:25])([O:20][CH2:18][CH3:19])=[O:22])=[C:6]([O:13][CH2:14][CH2:15][O:16][CH3:17])[N:5]=1To a suspension of lithium hydride (560 mg, 60 mmol) in dry dimethylformamide (DMF, 200 ml) was added 2-amino-6-methoxyethoxy purine (8.0 g, 40 mmol) [prepared according to the literature procedure: J. Kjellberg, M. Liljenberg and N. G. Johansson, Tetrahedron Lett. 877, 1986] and stirred for 60 min at 25° C. To this solution was added over 3 min a solution of 3-(diethylphosphonomethoxy)-1-bromopropane (12.0 g, 41.5 mmol) in DMF (5 mL) and the solution was heated at 55° C. for 4 h. The reaction mixture was then cooled to room temperature and water (50 mL) was added dropwise. Insoluble material was removed by filtration. The filtrate was concentrated in vacuo to give a viscous oil which was purified by column chromatography on silica gel (5% methanol in CH2 CL2) to afford 2-amino-9-[3-(diethylphosphonomethoxy)-propyl]-6-methoxyethoxy purine as a white crystalline solid: yield 3.45 g (21%); mp 78°-79° C.
불러오는 중…
