# US 4,394,516 A · Process for the preparation of a furan derivative

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- Number: US 4,394,516 A
- Document ID: US4394516A
- Status: Granted
- Kind: A
- Application number: 06/375,963
- Filed: 1982-05-07
- Granted: 1983-07-19
- Earliest claimed: 1981-05-07
- Assignees: Glaxo Group Limited
- Inventors: John W. Clitherow
- Web page: https://patentgrep.com/patent/US4394516A

## CPC

- C07D 307/52: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Ranitidine is prepared by reacting cystamine of formula (II) ##STR1## either with a nitroethenamine of formula (III) ##STR2## where L is a leaving group such as alkylthio, e.g. methylthio, or with a compound of formula (IV) ##STR3## where L is a leaving group as defined above, followed by reaction with methylamine, to give a disulphide of formula (V) ##STR4## which is then reacted with 5-[(dimethylamino)methyl]-2-furanmethanol under acid conditions.

## Claims

### Claim 1

A process for the preparation of ranitidine of formula (I) ##STR10## which comprises reacting cystamine of formula (II) ##STR11## either with a nitroethenamine of formula (III) ##STR12## where L is a leaving group, or with a compound of formula (IV) ##STR13## where L is a leaving group, followed by reaction with methylamine, to give a disulphide of formula (V) ##STR14## which is then reacted with 5-[(dimethylamino)methyl]-2-furanmethanol under acid conditions.

### Claim 2 (depends on 1)

A process as claimed in claim 1 wherein the reaction between the disulphide (V) and 5-[(dimethylamino)methyl]-2-furanmethanol is carried out at a temperature of 0.degree.-100.degree. C.

### Claim 3 (depends on 2)

A process as claimed in claim 2 wherein the reaction between the disulphide (V) and 5-[(dimethylamino)methyl]-2-furanmethanol is carried out in the presence of hydrochloric acid.

### Claim 4 (depends on 3)

A process as claimed in claim 3 wherein the reaction is carried out in the presence of concentrated hydrochloric acid at an initial temperature of 0.degree.-4.degree. C., with subsequent heating for a short period at 90.degree.-100.degree. C.

### Claim 5 (depends on 1)

A process as claimed in claim 1 wherein the disulphide (V) is prepared by reaction of cystamine and a nitroethenamine of formula (III) and this reaction is carried out in the presence of a suitable solvent.

### Claim 6 (depends on 5)

A process as claimed in claim 5, wherein the solvent is water.

### Claim 7 (depends on 1)

A process as claimed in claim 1 wherein L in the compounds of formulae (III) or (IV) is alkylthio and a steady stream of gas is passed through the reaction vessel during preparation of the disulphide.

### Claim 8 (depends on 1)

A process as claimed in claim 1 in which the compound of formula (I) is converted into an acid addition salt.

### Claim 9 (depends on 8)

A process as claimed in claim 8 in which the acid addition salt is the hydrochloride.