地西他滨杂质24

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

实验步骤: 1-O-Acetyl-3,5-di-O-(4-chloro-benzoyl)-2-deoxy-D-ribofuranose (3.603 Kg, 7.68 mol), 2-[(trimethylsilyl)amino]-4-[(trimethylsilyl)oxy]-s-triazine (1.970 Kg, 7.68 mol) and dichloromethane (71.6 Kg) were charged to a suitable reactor. The mixture was cooled to 0° C. TMSOTf (1.791 Kg, 8.06 mol) was added to the solution at 0° C. and stirred for 5 hours. 2M methyl amine in methanol solution (about 3.95 Kg) was then added to the mixture at 0° C. and stirred for 45 mins. The mixture was diluted with dichloromethane (71.6 Kg) and washed with saturated sodium bicarbonate solution (39.8 Kg) at 25° C. The organic layer was dried using molecule sieves (36 Kg). The molecule sieves were filtered and rinsed with dichloromethane (60.1 Kg). The organic layer was evaporated to dryness at 35° C. The solid was milled and vacuum dried at 45° C. to obtain 2.99 Kg (5.92 mol) of 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-β-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (compound Ib) in 52% HPLC purity (40% yield based on 1-O-acetyl-3,5-di-O-(4-chloro-benzoyl)-2-deoxy-D-ribofuranose) and 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-α-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (compound IVa) mixture in 27% HPLC purity. That α-anomer to β-anomer ratio was 1.0:1.91. stirred for 45 mins washed with saturated sodium bicarbonate solution (39.8 Kg) at 25° C The organic layer was dried The molecule sieves were filtered rinsed with dichloromethane (60.1 Kg) The organic layer was evaporated to dryness at 35° C The solid was milled vacuum dried at 45° C.

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

实验步骤: A mixture of MeCN (45 mL), 1-O-acetyl-3,5-di-O-(4-chlorobenzoyl)-2-deoxy-D-ribofuranose (3.0 g), 2-[(trimethylsilyl)amino]4-[(trimethylsilyl)oxy]-s-triazine (1.78 g) and TfOH (0.5 g) were stirred at about 0° C. for 24 hours. DMSO (6 mL) was added and the mixture was evaporated at 30˜50° C. under reduced pressure to remove the MeCN. A 29% solution of MeONa in MeOH (1.8 g, 9.9 mmol, 1.5 eq.) was added with stirring at about 20˜25° C. After the reaction was complete, MeOH was added to effect precipitation and the solid was filtered, washed and dried to give crude decitabine. API grade decitabine (>99.0 HPLC purity) is prepared by the recrystallization of crude decitabine from MeOH, followed by three washes with MeOH and drying at 40° C. under vacuum. the mixture was evaporated at 30˜50° C. under reduced pressure to remove the MeCN with stirring at about 20˜25° C the solid was filtered washed dried