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Synthesis method of celiprolol drug intermediate 3-(4-enthoxyphenyl)-1,1-diethylurea

A technology of ethoxyphenyl and diethylurea, which is applied in the field of synthesis of 3--1,1-diethylurea, a medicine intermediate of celilolol, can solve the problem that the vasodilation effect of isoproterenol cannot be reversed. and other problems, to achieve the effect of reducing intermediate links, reducing reaction temperature and reaction time, and improving reaction yield

Inactive Publication Date: 2016-04-20
CHENGDU DONG DIAN AI ER TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In healthy people, this product cannot reverse the vasodilation effect of isoproterenol mediated by β2 receptors

Method used

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  • Synthesis method of celiprolol drug intermediate 3-(4-enthoxyphenyl)-1,1-diethylurea

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0012] In a reaction vessel equipped with a stirrer and a dropping funnel, add 0.22mol of p-aminophenethyl ether (2), 0.45mol of sodium bisulfite, and 80ml of tetrahydrofuran, control the stirring speed at 130rpm, control the solution temperature at 35°C, and add N , N-diethylaminocarboxamide (3) 0.25mol, the dropwise addition time is controlled at 4h, and the stirring reaction is continued for 30h, adding 300ml of a 10% sodium chloride solution with a mass fraction of 25% oxalic acid solution to adjust the pH of the solution to 4. Continue to react for 4 hours, solids are precipitated, lower the solution temperature to 10°C, filter, wash with potassium nitrate solution, dehydrate activated alumina, and recrystallize in hexane to obtain 3-(4-ethoxyphenyl)-1 , 1-diethylurea (1) 43.09g, yield 83%.

example 2

[0014] In a reaction vessel equipped with a stirrer and a dropping funnel, add 0.22mol of p-aminophenethyl ether (2), 0.46mol of sodium bisulfite, and 85ml of tetrahydrofuran, control the stirring speed at 150rpm, control the solution temperature at 37°C, and add N , N-diethylaminocarboxamide (3) 0.26mol, the dropwise addition time is controlled at 4h, and the stirring reaction is continued for 33h, adding 320ml of a 12% sodium chloride solution with a mass fraction of 27% oxalic acid solution to adjust the pH of the solution to 4. Continue to react for 4 hours, solids are precipitated, reduce the temperature of the solution to 13°C, filter, wash with sodium sulfate solution, dehydrate phosphorus pentoxide, and recrystallize in hexane to obtain 3-(4-ethoxyphenyl)- 1,1-diethylurea (1) 44.65g, yield 86%.

example 3

[0016] In a reaction vessel equipped with a stirrer and a dropping funnel, add 0.22mol of p-aminophenethyl ether (2), 0.47mol of sodium bisulfite, and 90ml of tetrahydrofuran, control the stirring speed at 160rpm, control the solution temperature at 40°C, and add N , N-diethylaminocarboxamide (3) 0.27mol, the dropping time is controlled at 5h, and the stirring reaction is continued for 35h, adding 350ml of 15% sodium chloride solution with a mass fraction of 30% oxalic acid solution to adjust the pH of the solution to 5. Continue to react for 5 hours, solids are precipitated, reduce the temperature of the solution to 15°C, filter, wash with potassium nitrate solution, dehydrate activated alumina, and recrystallize in hexane to obtain 3-(4-ethoxyphenyl)-1 , 1-diethylurea (1) 47.25g, yield 91%.

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Abstract

A synthesis method of celiprolol drug intermediate 3-(4-enthoxyphenyl)-1,1-diethylurea comprises steps as follows: 0.22 mol of p-phenetidine, 0.45-0.47 mol of sodium hydrogen sulfite and 80-90 ml of tetrahydrofuran are added to a reaction container provided with a stirrer and a dropping funnel, the stirring speed is controlled within 130-160 rpm, the solution temperature is controlled within 35-40 DEG C, 0.25-0.27 mol of N,N-diethylamino formamide is dropwise added, the addition time is controlled within 4-5 h, the solution is stirred continuously to react for 30-35 h, 300-350 ml of a sodium chloride solution is added, the pH of the solution is adjusted to range from 4 to 5 with an oxalic acid, the solution reacts continuously for 4-5 h, solids are separated out, the solution is cooled to the temperature of 10-15 DEG C, filtration, washing with a salt solution, dehydration with a dehydrating agent and recrystallization in hexane are performed, and 3-(4-enthoxyphenyl)-1,1-diethylurea is obtained.

Description

technical field [0001] The invention relates to a synthesis method of celiprolol drug intermediate 3-(4-ethoxyphenyl)-1,1-diethylurea. Background technique [0002] Celylol has intrinsic sympathomimetic activity, does not increase airway resistance, expands peripheral blood vessels, and improves blood circulation. This product has no membrane stabilizing effect and does not inhibit myocardial contractility. It is less likely to cause sinus bradycardia than other β-blockers without endogenous sympathomimetic activity. The product can pass through the placental barrier. Suitable for mild to moderate hypertension. This product is a highly selective β-receptor blocker, which can dilate blood vessels and lower blood pressure by blocking β1 receptors. This product highly selectively binds to the β1 receptor on the myocardial cell membrane, and its affinity is 20 to 30 times stronger than that of the bronchial and vascular smooth muscle β2 receptor. It can reduce heart rate and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C273/18C07C275/34
CPCC07B2200/13C07C273/18C07C273/1809C07C275/34
Inventor 储冬红
Owner CHENGDU DONG DIAN AI ER TECH
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