反应 #466127

反应方程式

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

收率 6.0%

溶剂

phosphorus oxochloride

ethyl acetate

反应条件

后处理

1. 1
   温度is refluxed for about 30 minutes
2. 2
   其他After 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
   萃取The mixture is extracted with ethyl acetate (3×10 mL)
5. 5
   洗涤The combined organic layers are washed with brine
6. 6
   干燥dried over sodium fate
7. 7
   过滤filtered
8. 8
   浓缩concentrated
9. 9
   workup.DISSOLUTIONThe residue is dissolved in toluene (5 mL)
10. 10
    温度The reaction mixture is refluxed for about 16 hours
11. 11
    温度It is then cooled
12. 12
    洗涤washed with water (3×15 mL)
13. 13
    干燥The organic layer is dried over sodium sulfate
14. 14
    过滤filtered
15. 15
    浓缩concentrated
16. 16
    其他The residue is purified by preparative tlc

实验过程

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).

来源