반응 #466127

반응 방정식

1-(5-(4-fluorophenyl)thieno[3,2-b]pyridin-7-yl)piperidine-4-carboxamide

formic hydrazide

formic acid

→

5-(4-fluorophenyl)-7-[4-(1H-1,2,4-triazol-3-yl)-1-piperidinyl]thieno[3,2-b]pyridine

수율 6.0%

용매

phosphorus oxochloride

ethyl acetate

반응 조건

후처리

1. 1
   온도is refluxed for about 30 minutes
2. 2
   기타After the excess phosphorus oxychloride is removed under vacuum
3. 3
   workup.ADDITIONthe residue is treated with ethyl acetate (5 mL), and ice-water (10 mL)
4. 4
   추출The mixture is extracted with ethyl acetate (3×10 mL)
5. 5
   세척The combined organic layers are washed with brine
6. 6
   건조dried over sodium fate
7. 7
   여과filtered
8. 8
   농축concentrated
9. 9
   workup.DISSOLUTIONThe residue is dissolved in toluene (5 mL)
10. 10
    온도The reaction mixture is refluxed for about 16 hours
11. 11
    온도It is then cooled
12. 12
    세척washed with water (3×15 mL)
13. 13
    건조The organic layer is dried over sodium sulfate
14. 14
    여과filtered
15. 15
    농축concentrated
16. 16
    기타The residue is purified by preparative tlc

실험 절차

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).

출처