反应详情

温度

50 °C

A solution of 2-[4-(2-acetylamino-4-methyl-thiazole-5-sulfonylamino)-phenyl]-N-[6-amino-1-cyclopropylmethyl-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetamide (56 mg, 0.085 mmol) in methanol warmed to 50° C. was treated with a 10% aqueous sodium hydroxide solution (0.34 mL, 0.085 mmol). The reaction was stirred at 50° C. for 6 h. At this time, the reaction was concentrated in vacuo, diluted with water, and acidified to pH=2 with a 1.0N aqueous hydrochloric acid solution (0.9 mL). This mixture was cooled in an ice-bath. The resulting solids were collected by filtration, washed with water, and dried in vacuo. HPLC (20–80% acetonitrile/water) afforded N-(5-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenylsulfamoyl}-4-methyl-thiazol-2-yl)-acetamide (16.1 mg, 29.7%) as a white solid; FAB-HRMS m/e calculated for C29H28FN7O5S2 (M+H)+ 638.1656, found 638.1641; and 2-amino-4-methyl-thiazole-5-sulfonic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-amide trifluoro-acetic acid salt (5.4 mg, 10%) as a white solid; FAB-HRMS m/e calculated for C27H26FN7O4S2 (M+H)+ 596.1550, found 596.1547.

1. concentrationAt this time, the reaction was concentrated in vacuo
2. additiondiluted with water
3. temperatureThis mixture was cooled in an ice-bath
4. filtrationThe resulting solids were collected by filtration
5. washwashed with water
6. customdried in vacuo