5-(2-溴甲基)-2,2-二甲基-1,3-二氧六环

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of uracil (88.5 g, 0.79 mol) in dry DMF (250 mL) was added cesium carbonate (171 g, 0.527 mol) at RT and stirred at the same temperature for 30 min. To the above reaction mixture was added a solution of compound 33 (117 g, 0.527 mol) in dry DMF (250 mL) over a period of 30 min and heated at 50° C. for 24 h. The reaction mixture was filtered, filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform) to give the title compound (60 g, 45%). TLC: Chloroform/Methanol, 4:1, Rf=0.3 The reaction mixture was filtered filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of uracil (88.5 g, 0.79 mol) in dry DMF (250 mL) was added cesium carbonate (171 g, 0.527 mol) at RT and stirred at the same temperature for 30 min. To the above reaction mixture was added a solution of compound 33 (117 g, 0.527 mol) in dry DMF (250 mL) over a period of 30 min and heated at 50° C. for 24 h. The reaction mixture was filtered, filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform) to give the title compound (60 g, 45%). TLC: Chloroform/Methanol, 4:1, Rf=0.3 The reaction mixture was filtered filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of compound 32 (84 g, 0.528 mol) in dry DMF (500 mL) was added triphenylphosphine (207 g, 0.79 mol) with vigorous stirring until it becomes a clear solution. The mixture was cooled to 0° C. and added CBr4 (260 g, 0.79 mol) portion wise over a period of 30 min and allowed to stir at RT for 5 h. The reaction mixture was cooled to 0° C., added saturated NaHCO3 solution (200 mL) and extracted with hexane (4×200 mL). The combined organic layer was dried, concentrated under vacuum and the crude title compound (117 g) was used for next reaction without any purification. TLC: Pet. ether/EtOAc, 7:3, Rf=0.6 to stir at RT for 5 h The reaction mixture was cooled to 0° C. extracted with hexane (4×200 mL) The combined organic layer was dried concentrated under vacuum the crude title compound (117 g) was used for next reaction without any purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 2-amino-6,8-dichloropurine (0.82 g), 5-bromoethyl-2,2-dimethyl-1,3-dioxan (0.9 g) and anhydrous potassium carbonate (0.83 g) in N,N-dimethylformamide (20 ml) was stirred at room temperature for 18 hours under dry nitrogen. The mixture was then filtered and the filtrate evaporated. The residue was purified by column chromatography on silica (100 g) [eluent 2% methanol-dichloromethane] to give 2-amino-6,8-dichloro-9-(2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl)purine (t.l.c. r.f. 0.50, 5% methanol-dichloromethane) as a pale solid (0.62 g, 45%). Recrystallisation from diethyl ether gave an off-white solid m.p. 149°-150° C. The mixture was then filtered the filtrate evaporated The residue was purified by column chromatography on silica (100 g) [eluent 2% methanol-dichloromethane]

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxane (15) (M. R. Harnden et al, J. Med. Chem., 30, 1636, 1987) (12.0 gm, 53.81 mmol) in dry DMF (150 ml) were added uracil (7.0 gm, 62.4 mmol) and potassium carbonate (14.0 gm). The reaction mixture was stirred at 25° C. for 5 days. The resulting solution was filtered and the solvent removed. The residue obtained was purified by column chromatography on silica gel eluting with chloroform-methanol (90:10, v/v) to afford 17 (4.0 gm, 25.2%). The resulting solution was filtered the solvent removed The residue obtained was purified by column chromatography on silica gel eluting with chloroform-methanol (90:10

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of uracil (88.5 g, 0.79 mol) in dry DMF (250 mL) was added cesium carbonate (171 g, 0.527 mol) at RT and stirred at the same temperature for 30 min. To the above reaction mixture was added a solution of compound 33 (117 g, 0.527 mol) in dry DMF (250 mL) over a period of 30 min and heated at 50° C. for 24 h. The reaction mixture was filtered, filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform) to give the title compound (60 g, 45%). TLC: Chloroform/Methanol, 4:1, Rf=0.3 The reaction mixture was filtered filtrate concentrated under vacuum and crude purified by column chromatography over silica gel (3% methanol in chloroform)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of compound 32 (84 g, 0.528 mol) in dry DMF (500 mL) was added triphenylphosphine (207 g, 0.79 mol) with vigorous stirring until it becomes a clear solution. The mature was cooled to 0° C. and added CBr4 (260 g, 0.79 mol) portion wise over a period of 30 min and allowed to stir at RT for 5 h. The reaction mixture was cooled to 0° C., added saturated NaHCO3 solution (200 mL) and extracted with hexane (4×200 mL). The combined organic layer was dried, concentrated under vacuum and the crude title compound (117 g) was used for next reaction without any purification. TLC: Pet. ether/EtOAc, 7:3, Rf=0.6 to stir at RT for 5 h The reaction mixture was cooled to 0° C. extracted with hexane (4×200 mL) The combined organic layer was dried concentrated under vacuum the crude title compound (117 g) was used for next reaction without any purification

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-(2-bromoethyl)-2,2-dimethyl-1,3-dioxane (15) (M. R. Hamden et al, J. Med. Chem., 30, 1636, 1987) (12.0 gm, 53.81 mmol) in dry DMF (150 ml) were added uracil (7.0 gm, 62.4 mmol) and potassium carbonate (14.0 gm). The reaction mixture was stirred at 25° C. for 5 days. The resulting solution was filtered and the solvent removed. The residue obtained was purified by column chromatography on silica gel eluting with chloroform-methanol (90:10, v/v) to afford 17 (4.0 gm, 25.2%). The resulting solution was filtered the solvent removed The residue obtained was purified by column chromatography on silica gel eluting with chloroform-methanol (90:10