反应 #1885092

反应方程式

methyl 3-hydrazinylthiophene-2-carboxylate

3c

Ethyl 4-chloro-6,7-difluoro-quinoline-3-carboxylate

→

compound 41

7,8-Difluoro-2-(thiophen-3-yl)-2,5-dihydro-pyrazolo-[4,3-c]quinolin-3-one

溶剂

ethanol

反应条件

后处理

1. 1
   浓缩the solution was concentrated in vacuo and residue
2. 2
   workup.DISSOLUTIONwas dissolved in chloroform
3. 3
   洗涤washed with aq. Sodium bicarbonate solution
4. 4
   其他dried
5. 5
   浓缩concentrated in vacuo
6. 6
   workup.STIRRINGstirred with 1N sodium hydroxide solution for 30 minutes
7. 7
   浓缩concentrated in vacuo
8. 8
   过滤The solid was filtered
9. 9
   洗涤washed with water
10. 10
    其他dried
11. 11
    workup.ADDITION1N sodium hydroxide was added
12. 12
    温度the reaction mixture was refluxed for 1 hr
13. 13
    过滤the crystals were collected by filtration
14. 14
    workup.STIRRINGstirred at 190° C. for 1 hour
15. 15
    其他The copper was removed by filtration
16. 16
    workup.ADDITIONthe filtrate was mixed with 1N sodium hydroxide solution
17. 17
    萃取followed by extraction with ether
18. 18
    workup.ADDITIONThe separated aqueous layer was treated with active charcoal

实验过程

1.05 equiv. of methyl 3-hydrazinylthiophene-2-carboxylate was added to a solution of 3c in ethanol. After 1.5 hr of stirring at room temperature, the solution was concentrated in vacuo and residue was dissolved in chloroform and washed with aq. Sodium bicarbonate solution, dried and concentrated in vacuo. The resulting solid was suspended in ethanol and stirred with 1N sodium hydroxide solution for 30 minutes, acidified with acetic acid and concentrated in vacuo. The solid was filtered, washed with water, dried and suspended in ethanol. 1N sodium hydroxide was added and the reaction mixture was refluxed for 1 hr, acidified with acetic acid and the crystals were collected by filtration. The yellow solid was combined with copper powder and quinoline and stirred at 190° C. for 1 hour. The copper was removed by filtration and the filtrate was mixed with 1N sodium hydroxide solution, followed by extraction with ether. The separated aqueous layer was treated with active charcoal, acidified with acetic acid to yield compound 41 as yellow solid. 1H-NMR (DMSO-d6) δ (ppm):7.58 (1H, dd, J=5.22, 3.30 Hz), 7.69 (1H, dd, J=11.26, 7.14 Hz), 7.74 (1H, dd, J=5.22, 1.38 Hz), 7.80 (1H, m), 8.15 (1H, dd, J=10.7, 8.2 Hz), 8.77 (1H, d, J=6.2 Hz). m/z 304.2 (MH+).

来源