反应详情

A suspension of 1-(5-(4-fluorophenyl)thieno[3,2-b]pyridin-7-yl)piperidine-4-carboxamide (100 mg, 0.32 mmole) in phosphorus oxochloride (5 mL) is refluxed for about 30 minutes. After the excess phosphorus oxychloride is removed under vacuum, the residue is treated with ethyl acetate (5 mL), and ice-water (10 mL). The mixture is extracted with ethyl acetate (3×10 mL). The combined organic layers are washed with brine, dried over sodium fate, filtered, and concentrated. The residue is dissolved in toluene (5 mL) and then formic hydrazide (100 mg, 1.7 mmole) and formic acid (0.05 mL) are added. The reaction mixture is refluxed for about 16 hours. It is then cooled, diluted with ethyl acetate (15 mL), and washed with water (3×15 mL). The organic layer is dried over sodium sulfate, filtered, and concentrated. The residue is purified by preparative tlc to give 5-(4-fluorophenyl)-7-[4-(1H-1,2,4-triazol-3-yl)-1-piperidinyl]thieno[3,2-b]pyridine (7 mg, 6% yield) as a white solid. This material is dissolved in ethyl acetate (1 mL), saturated with HCl (2 mL), and then concentrated to afford 5-(4-Fluorophenyl)-7-[4-(4H-1,2,4-triazol-3-yl)piperidyl]thioheno[3,2-b]pyridine hydrochloride (compound 2) as greasy oil. Trituration with ether, filtration and drying in vacuo affords the desired product as a solid. m.p. >300° C. (dec).

1. temperatureis refluxed for about 30 minutes
2. customAfter the excess phosphorus oxychloride is removed under vacuum
3. additionthe residue is treated with ethyl acetate (5 mL), and ice-water (10 mL)
4. extractionThe mixture is extracted with ethyl acetate (3×10 mL)
5. washThe combined organic layers are washed with brine
6. dry with materialdried over sodium fate
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe residue is dissolved in toluene (5 mL)
10. temperatureThe reaction mixture is refluxed for about 16 hours
11. temperatureIt is then cooled
12. washwashed with water (3×15 mL)
13. dry with materialThe organic layer is dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue is purified by preparative tlc