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High-purity clomipramine hydrochloride and preparation method thereof

A technology of clomipramine hydrochloride and clomipramine, which is applied in the field of preparing tricyclic antidepressant clomipramine hydrochloride, and can solve problems such as limited technical literature

Active Publication Date: 2022-03-25
HUNAN DONGTING PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Although clomipramine hydrochloride has been used clinically for more than 30 years, its technical literature is still quite limited, for example, people still expect a new method for the preparation of clomipramine hydrochloride

Method used

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  • High-purity clomipramine hydrochloride and preparation method thereof
  • High-purity clomipramine hydrochloride and preparation method thereof
  • High-purity clomipramine hydrochloride and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0079] (1) preparation of intermediate I:

[0080]

[0081] (2) Preparation of Intermediate II:

[0082]

[0083] (3) preparation of clomipramine:

[0084]

[0085] (4) preparation of clomipramine hydrochloride crude product:

[0086]

[0087] (5) preparation of clomipramine hydrochloride refined product:

[0088]

Embodiment 1

[0089] Example 1: Preparation of clomipramine hydrochloride

[0090] (1) preparation of intermediate I:

[0091] 1 part by weight of 1,3-bromochloropropane was added to the reaction flask, 1.2 parts by weight of 40% dimethylamine aqueous solution was added dropwise under stirring, and stirring was performed for 35 minutes after the addition, and then 1.2 parts by weight was added dropwise at 25°C. 40% sodium hydroxide solution of 40%, after adding, keep stirring for 4h,

[0092] After the completion of the reaction, let stand, divide the alkaline water layer of the lower layer, the upper layer liquid is acidified to pH 2.5 with concentrated hydrochloric acid, then stirred for 15 minutes, and the lower layer liquid is left to stand, and then the upper layer liquid is used sodium hydroxide solution (concentration 1~2mol. / L) liquid is alkalized to pH to 12, after adding, leave standstill, divide the alkaline water layer of the lower layer, the upper layer is the intermediate I...

Embodiment 2

[0106] Example 2: Preparation of clomipramine hydrochloride

[0107] (1) preparation of intermediate I:

[0108] 1 part by weight of 1,3-bromochloropropane was added to the reaction flask, 0.8 part by weight of 40% aqueous dimethylamine solution was added dropwise under stirring, and after the addition was completed, the mixture was stirred for 40 minutes, and then 1 weight part was added dropwise at 15°C. 40% sodium hydroxide solution of 40%, after adding, keep stirring for 5h.

[0109] After the completion of the reaction, let stand, divide the alkaline water layer of the lower layer, the upper layer liquid is acidified to pH 2 with concentrated hydrochloric acid, then stirred for 10 minutes, and the lower layer liquid is left to stand, and then the upper layer liquid is used sodium hydroxide solution (concentration 1~2mol. 1 / L) liquid is alkalized to pH to 11, leave standstill after adding, divide the alkaline water layer of the lower layer, the upper layer is the interm...

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Abstract

The invention relates to high-purity clomipramine hydrochloride and a preparation method thereof. Specifically, the preparation method includes the following steps: reacting bromochloropropane and dimethylamine in the presence of a base to obtain an intermediate I compound; adding sangite and potassium hydroxide to toluene, heating and reacting to obtain intermediate II Add potassium carbonate, potassium hydroxide to the intermediate II, heat the reactant, then add the mixed solution of the intermediate I product and toluene, continue the heating reaction to complete, then make the reaction liquid cooling, add water to extract, obtain the compound containing clomipramine The organic layer of the previous product was concentrated under reduced pressure to obtain an oil, added acetone, then added dropwise hydrochloric acid to acidify, then crystallized, centrifuged to obtain crystals, and dried to obtain the crude product of clomipramine hydrochloride; the obtained clomipramine hydrochloride Put the crude product and solvent into the reaction kettle, heat to dissolve, then add medicinal charcoal to reflux for decolorization, filter to decarbonize, cool and crystallize, filter to collect crystals, and dry to obtain the finished product of clomipramine hydrochloride. The method of the present invention exhibits the effects described in the specification.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a method for preparing an antipsychotic drug clomipramine, particularly a medicinal salt thereof, and more particularly to a method for preparing a tricyclic antidepressant clomipramine hydrochloride. The method for preparing clomipramine hydrochloride of the present invention exhibits excellent technical effects as described below. Background technique [0002] Clomipramine, Clomipramine, CAS: 303-49-1, molecular formula: C19H23ClN2, molecular weight: 314.85, its hydrochloride is commonly used in clinical practice, the chemical information of clomipramine hydrochloride is as follows: [0003] [0004] The chemical name is N,N-dimethyl 10,11-dihydro-3-chloro-5H-dibenzo[b,f]azepine-5-propylamine hydrochloride. Also known as 3-chloro-5-(3-dimethylaminopropyl)-10,11-dihydro-5H-dibenzo(6,5)azepine hydrochloride. Clomipramine hydrochloride is a white to slightly yellow crystalline...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D223/28
CPCC07D223/28C07B2200/13
Inventor 侯奇伟王波赵国权刘源徐坤鑫
Owner HUNAN DONGTING PHARMA