反应详情

A mixture of 2.06 g. of 2,3-dimethylvaleric acid (15.8 mmol). in 30 ml. of methylene chloride was cooled in a cold water bath and treated with 2.0 g. of oxalyl chloride (15.8 mmol.). The resulting solution was stirred at room temperature for 2 hours, then the methylene chloride was removed under reduced pressure. The resulting residue was added dropwise to a cold, stirred suspension of 1.2 g. of 7-chloro-4-(4-chlorophenyl)-2-(hydroxymethyl)-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one (3.1 mmol.) in 25 ml. of pyridine. After stirring for 35 minutes, the mixture was poured onto ice-water and allowed to stand for 16 hours at room temperature, resulting in the formation of a yellow precipitate, which was collected, washed with water, air-dried, then purified using flash chromatography on silica gel, employing a mixture of 5% ethyl acetate: 95% methylene chloride as the eluent. Fractions containing the product were combined and triturated with ether to yield 7-chloro-4-(4-chlorophenyl)-2-[(2,3-dimethyl-1-oxopentoxy)methyl]-5H-pyrido[3,4-b][1,4]benzothiazin-3(2H)-one as a pale yellow crystalline solid (1.18 g; 76% yield) having the structural formula, ##STR22## a melting point in the range of 165°-173° C. and the following elemental analysis:

1. additionA mixture of 2.06 g
2. additiontreated with 2.0 g
3. customthe methylene chloride was removed under reduced pressure
4. additionThe resulting residue was added dropwise to a cold
5. stirringstirred
6. additionsuspension of 1.2 g
7. stirringAfter stirring for 35 minutes
8. additionthe mixture was poured onto ice-water
9. waitto stand for 16 hours at room temperature
10. customresulting in the formation of a yellow precipitate, which
11. customwas collected
12. washwashed with water
13. customair-dried
14. custompurified
15. additiona mixture of 5% ethyl acetate
16. additionFractions containing the product
17. customtriturated with ether