Unlock instant, AI-driven research and patent intelligence for your innovation.

The preparation method of almotriptan intermediate 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine

A technology of pyrrolidinylsulfonylmethyl and almotriptan is applied in the field of preparation of 4-phenylhydrazine as an intermediate of almotriptan, and can solve the problem of decreased product yield, layered emulsification, and opacity of tin salt and other problems to achieve the effect of easy layering

Active Publication Date: 2017-12-05
CHONGQING PHARSCIN PHARM CO LTD
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inventor also found that when the amount of water added to the system was less than 50 times, the emulsified tin salt and layered emulsification would still occur, and when the amount of water added to the system exceeded 80 times, the product yield would decline significantly

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • The preparation method of almotriptan intermediate 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine
  • The preparation method of almotriptan intermediate 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine
  • The preparation method of almotriptan intermediate 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Preparation of 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine (post-treatment adds 60 times of water)

[0030] Put 5.0kg of 4-aminobenzenesulfonylpyrrolidine, 51.0kg of concentrated hydrochloric acid, and 43.0kg of water into the reaction kettle 1. After feeding, start to cool down to the temperature of the material at -15°C to -20°C; The prepared solution of sodium nitrite 1.53kg / water 26.0kg, after the dropwise addition, was incubated and stirred for 30 minutes to obtain a diazotization solution.

[0031] Put 20.0kg of concentrated hydrochloric acid and 23.6kg of tin protochloride into the reaction kettle 2. After the feeding is completed, start to cool down to a material temperature of -15°C to -20°C; then start to drop the diazotization solution obtained above, After the dropwise addition, the reaction was incubated for 1 h.

[0032] After the reaction was completed, 300 kg of water was added to the reaction system, and the pH of the system was adjusted...

Embodiment 2

[0033]Example 2 Preparation of 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine (post-treatment adds 65 times of water)

[0034] Put 5.0kg of 4-aminobenzenesulfonylpyrrolidine, 51.0kg of concentrated hydrochloric acid, and 43.0kg of water into the reaction kettle 1. After feeding, start to cool down to the temperature of the material at -15°C to -20°C; The prepared solution of sodium nitrite 1.53kg / water 26.0kg, after the dropwise addition, was incubated and stirred for 30 minutes to obtain a diazotization solution.

[0035] Put 20.0kg of concentrated hydrochloric acid and 23.6kg of tin protochloride into the reaction kettle 2. After the feeding is completed, start to cool down to a material temperature of -15°C to -20°C; then start to drop the diazotization solution obtained above, After the dropwise addition, the reaction was incubated for 1 h.

[0036] After the reaction was completed, 325 kg of water was added to the reaction system, and the pH of the system was adjusted ...

Embodiment 3

[0037] Example 3 Preparation of 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine (add 70 times of water for post-treatment)

[0038] Put 5.0kg of 4-aminobenzenesulfonylpyrrolidine, 51.0kg of concentrated hydrochloric acid, and 43.0kg of water into the reaction kettle 1. After feeding, start to cool down to the temperature of the material at -15°C to -20°C; The prepared solution of sodium nitrite 1.53kg / water 26.0kg, after the dropwise addition, was incubated and stirred for 30 minutes to obtain a diazotization solution.

[0039] Put 20.0kg of concentrated hydrochloric acid and 23.6kg of stannous chloride into the reaction kettle 2. After the feeding is completed, start to cool down to the temperature of the material at -15°C to -20°C; then start to drop the diazotization solution obtained above, drop After the end, heat preservation reaction 1h.

[0040] After the reaction was completed, 350 kg of water was added to the reaction system, and the pH of the system was adjusted t...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of almotriptan malate intermediate 4-(1-pyrrolidyl sulfomethyl)-phenylhydrazine. The method comprises the following steps: performing diazotization and reduction reaction on 4-aminophenylmethane sulfonyl pyrrolidine serving an initial raw material, then adding water of which the weight is 60 to 70 times that of the initial raw material, and performing post treatment, and thus finally, obtaining the 4-(1-pyrrolidyl sulfomethyl)-phenylhydrazine. The method is simple in operation, high in yield and suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the field of organic chemistry and medicinal chemistry, and in particular relates to a preparation method of almotriptan intermediate 4-(1-pyrrolidinylsulfonylmethyl)-phenylhydrazine. Background technique [0002] Almotriptan (Almotriptan), the chemical name is 3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, which is Spanish Emero 5-HT developed by the company 1B / 1D Receptor agonists for the treatment of migraine with or without aura. [0003] The pathogenesis of migraine is still unclear, but it has been confirmed that the large intracranial blood vessels dilate during headache, and migraine may be mainly related to the stimulation of 5-HT 1B / 1D related to the receptor. Compounds such as ergotamines and 5-HT produce vasoconstriction by stimulating 5-HT1 receptors, but these compounds have poor selectivity and thus have relatively large side effects. In September 2000, Almotriptan Malate was launched...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/26
CPCC07D295/26
Inventor 魏洪岗张奥吴科范林王道权
Owner CHONGQING PHARSCIN PHARM CO LTD