تفاعل #466127

معادلة التفاعل

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

المردود 6.0%

المذيبات

phosphorus oxochloride

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةis refluxed for about 30 minutes
2. 2
   أخرىAfter 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
   استخلاصThe mixture is extracted with ethyl acetate (3×10 mL)
5. 5
   غسيلThe combined organic layers are washed with brine
6. 6
   تجفيفdried over sodium fate
7. 7
   ترشيحfiltered
8. 8
   تركيزconcentrated
9. 9
   workup.DISSOLUTIONThe residue is dissolved in toluene (5 mL)
10. 10
    درجة الحرارةThe reaction mixture is refluxed for about 16 hours
11. 11
    درجة الحرارةIt is then cooled
12. 12
    غسيلwashed with water (3×15 mL)
13. 13
    تجفيفThe organic layer is dried over sodium sulfate
14. 14
    ترشيحfiltered
15. 15
    تركيزconcentrated
16. 16
    أخرىThe residue is purified by preparative tlc

الإجراء التجريبي

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).

المصدر