反应 #324294

反应方程式

sodium hydroxide

1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol

4-chloro-5-chloromethyl-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]-pyridine

water

→

4-Chloro-5-[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine, hydrochloride

溶剂

tetrahydrofuran

tetrahydrofuran

反应条件

后处理

1. 1
   其他In a three necked flask (250 ml.), fitted with a stirrer
2. 2
   温度reflux condenser and gas inlet tube
3. 3
   workup.ADDITIONare introduced 24.4 g
4. 4
   温度the solution is cooled to 45°
5. 5
   workup.ADDITIONare added 6.43 g
6. 6
   温度To the mixture, which is warmed to 50°
7. 7
   其他within 3 minutes
8. 8
   其他Then the warm mixture is transferred into a separating funnel
9. 9
   萃取the lower aqueous sodium hydroxide is extracted with 10 ml
10. 10
    干燥The combined tetrahydrofuran layers are dried by means of sodium sulfate
11. 11
    其他after the solvent has been removed the residual oil
12. 12
    萃取is extracted with ether
13. 13
    workup.ADDITIONtreated with charcoal
14. 14
    过滤filtered
15. 15
    workup.ADDITIONTo the solution of free base are added dropwise 5.9 ml
16. 16
    过滤The precipitated 4-chloro-5[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]- 1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine, hydrochloride is filtered off
17. 17
    其他dried in the vacuum desiccator
18. 18
    其他recrystallized from acetonitrile, m.p. 200°-201°

实验过程

In a three necked flask (250 ml.), fitted with a stirrer, reflux condenser and gas inlet tube are introduced 24.4 g. of sodium hydroxide (0.61 mol.) and 23 ml. of water. While passing nitrogen through the flask, the solution is cooled to 45° and then are added 6.43 g. of 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol (0.025 mol.), [prepared according to J. Med. Chem., Vol. 12, 784 (1969)], 0.43 g. of benzyltrimethylammonium chloride and 25 ml. of tetrahydrofuran. To the mixture, which is warmed to 50°, a solution of 6.1 g. of 4-chloro-5-chloromethyl-1-ethyl-3-methyl-1H-pyrazolo[3,4-b]-pyridine (0.025 mol.) in 10 ml. of tetrahydrofuran is added from a prewarmed dropping funnel within 3 minutes. The mixture is stirred vigorously for 3 hours at 60° using a water bath. Then the warm mixture is transferred into a separating funnel, the lower aqueous sodium hydroxide is extracted with 10 ml. of tetrahydrofuran. The combined tetrahydrofuran layers are dried by means of sodium sulfate and after the solvent has been removed the residual oil is extracted with ether, treated with charcoal and filtered. To the solution of free base are added dropwise 5.9 ml. of ethereal hydrochloric acid (30.9%). The precipitated 4-chloro-5[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]- 1-ethyl-3-methyl-1H-pyrazolo[3,4-b]pyridine, hydrochloride is filtered off, dried in the vacuum desiccator and recrystallized from acetonitrile, m.p. 200°-201°; yield 5.67 g. (45%).

来源