反应详情

温度

150 °C

A solution of 4-fluorobenzenesulfonic acid 2-butyrylaminobenzothiazol-6-yl ester (intermediate 78) (135 mg, 0.34 mmol) and 1-amino-2-methylpropan-2-ol (153 mg, 1.718 mmol) in 3 ml of N-methylpyrrolidone in a 5 ml microwave vial, equipped with a magnetic bar, is heated for 20 minutes at 150° C. by microwave. The reaction medium is extracted with ethyl acetate (3×20 ml) and washed with water (4×25 ml). The organic phase is dried over magnesium sulfate, filtered and then evaporated to dryness. The residue obtained is purified by chromatography on silica, on an 8 g 15-35 μm AIT column, eluting with a 9/1 ethyl acetate/cyclohexane mixture. After evaporating off the solvent, 55 mg of a colorless solid are obtained. The product is dissolved in a minimum amount of dioxane, and 4 N hydrochloric acid dissolved in dioxane is added. The precipitate obtained is filtered off by suction, washed with dioxane and then dried under vacuum at 40° C. to give 42 mg of 4-(2-hydroxy-2-methylpropylamino)benzenesulfonic acid 2-butyrylaminobenzothiazol-6-yl ester hydrochloride, i.e. a yield of 25%.

1. extractionThe reaction medium is extracted with ethyl acetate (3×20 ml)
2. washwashed with water (4×25 ml)
3. dry with materialThe organic phase is dried over magnesium sulfate
4. filtrationfiltered
5. customevaporated to dryness
6. customThe residue obtained
7. customis purified by chromatography on silica, on an 8 g 15-35 μm AIT column
8. washeluting with a 9/1 ethyl acetate/cyclohexane mixture
9. customAfter evaporating off the solvent, 55 mg of a colorless solid
10. customare obtained
11. additionis added
12. customThe precipitate obtained
13. filtrationis filtered off by suction
14. washwashed with dioxane
15. customdried under vacuum at 40° C.