反应详情

A solution of 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16) (500 mg, 1.14 mmol), propionic acid (253 mg, 3.42 mmol), HBTU (1.23 g, 3.42 mmol) and N,N-diisopropylamine (737 mg, 5.7 mmol) in 6.5 ml of dimethylformamide is stirred overnight at room temperature. The reaction medium is evaporated to dryness. The dry residue is extracted twice with 50 ml of ethyl acetate and washed with water. The organic phase is then washed with saturated sodium chloride solution. The organic phase is dried over magnesium sulfate and then evaporated. The oil obtained is dissolved in 35 ml of dimethyl sulfoxide and then purified 7 times by preparative HPLC on a Nucléodur C18, 100′10 μm reverse-phase column with a gradient over 52 minutes of 5% to 95% acetonitrile supplemented with 0.07% trifluoroacetic acid in water, supplemented with 0.07% trifluoroacetic acid. The flow rate is 70 ml/min. The fractions containing the clean product are concentrated to give 300 mg of 4-fluorobenzenesulfonic acid 2-propionylaminobenzothiazol-6-yl ester in a yield of 69%.

1. customThe reaction medium is evaporated to dryness
2. extractionThe dry residue is extracted twice with 50 ml of ethyl acetate
3. washwashed with water
4. washThe organic phase is then washed with saturated sodium chloride solution
5. dry with materialThe organic phase is dried over magnesium sulfate
6. customevaporated
7. customThe oil obtained
8. custompurified 7 times by preparative HPLC on a Nucléodur C18, 100′10 μm reverse-phase column with a gradient over 52 minutes of 5% to 95% acetonitrile
9. additionThe fractions containing the clean product
10. concentrationare concentrated