[go: up one dir, main page]

GB2067991A - Process for the Preparation of a Furan Derivative - Google Patents

Process for the Preparation of a Furan Derivative Download PDF

Info

Publication number
GB2067991A
GB2067991A GB8100477A GB8100477A GB2067991A GB 2067991 A GB2067991 A GB 2067991A GB 8100477 A GB8100477 A GB 8100477A GB 8100477 A GB8100477 A GB 8100477A GB 2067991 A GB2067991 A GB 2067991A
Authority
GB
United Kingdom
Prior art keywords
formula
methyl
group
thiol
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
GB8100477A
Other versions
GB2067991B (en
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Glaxo Group Ltd
Original Assignee
Glaxo Group Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd
Priority to GB8100477A priority Critical patent/GB2067991B/en
Publication of GB2067991A publication Critical patent/GB2067991A/en
Application granted granted Critical
Publication of GB2067991B publication Critical patent/GB2067991B/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
    • C07D203/12—Radicals substituted by nitrogen atoms not forming part of a nitro radical

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Furan Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a process for the preparation of ranitidine of formula (I> <IMAGE> which comprises reacting a thiol of formula (II> <IMAGE> with an alkylating agent of formula (III> <IMAGE> where R1 is the group -CH2CH2L, in which L is a leaving group, and R2 is a hydrogen atom, or R1 and R2, together with the nitrogen atom to which they are attached form an ethyleneimino group; and to intermediates for the said process.

Description

SPECIFICATION Process for the Preparation of a Furan Derivative This invention relates to a process for the preparation of a furan derivative.
The furan derivative of formula (I)
which is known as ranitidine is disclosed in British Patent Specification No. 1 565966 as a potent and selective H2-antagonist.
The present invention provides a process for the preparation of the furan derivative of formula (l) which comprises reacting a thiol of formula (II)
with an alkylating agent of formula (III)
where R1 is the group-CH2CH 2L, in which L is a leaving group, and R2 is a hydrogen atom, or R, and R2, together with the nitrogen atom to which they are attached, form an ethyleneimino group.
An example of a suitable leaving group L is a halogen atom, chlorine being preferred.
The process of the present invention provides a novel and useful method of the preparation of the compound ranitidine.
When R, is the groupCH2C:H2L and R2 is a hydrogen atom the process according to the invention may be carried out in a suitable solvent such as water, aqueous tetrahydrofuran, dimethylformamide, an alkanoi (e.g. methanol) or a ketonic solvent such as acetone optionally with the addition of water. The reaction is preferably carried out in the presence of a base such as an inorganic base (e.g. an alkali metal carbonate or hydroxide such as potassium carbonate or potassium or sodium hydroxide), an alkoxide (e.g. sodium methoxide) or a tertiary amine (e.g. triethylamine), and at a suitable temperature for example within the range of 10 to 800C. The reaction is preferably effected in an inert atmosphere, for example under nitrogen.In a modification of this process the thiol of formula (II) may be reacted with the alkylating agent (Ill) in a two phase system using for example chloroform and water, in the presence of a phase transfer catalyst (e.g. a quaternary ammonium salt such as benzyltriethylanimonium chloride) and a base (e.g. sodium hydroxide).
Particularly advantageous conditions for carrying out the alkylation reaction include treating the thiol of formula (II) with the alkyating reagent (Ill) (in which R is the group -CH2CH2Cl and R2 is a hydrogen atom) neither in the presence of an alkali metal hydroxide (e.g. potassium hydroxide) in water, "or in the presence of potassium carbonate using aqueous tetrahydrofuran as the solvent.
Advantageously the reaction is carried out at room temperature under an atmosphere of nitrogen.
When R and Together with the nitrogen atom to which they are attached form an ethyleneimino group the reaction may be carried out in the absence or presence of a solvent. Suitable solvents include water, an alkanol (e.g. methanol) or dimethylformamide. The reaction is preferably carried out with heating, for example at 1 000C, and in an inert atmosphere, for example under nitrogen.
The thiol (11) may be used directly or is generated in situ from an acid addition salt such as oxalate salt. Alternatively, when the reaction is carried out in the presence of a base, the thiol (il) may be generated in situ from the isothiourea (IV) or a salt thereof, for example a bis maleate salt, under the basic conditions of the reaction.
The thiol of formula (II) may be prepared by reacting the corresponding alcohol of formula (V)
with thiourea in the presence of a concentrated acid such as concentrated hydrochloric acid to produce the isothiourea (IV), which is then converted into the thiol of formula (II) by treatment with a base such as sodium carbonate or 5N sodium hydroxide, preferably in the presence of an antioxidant such as sodium dithionate or sodium metabisulphite. Once isolated, the free base thus formed may be converted into a stable acid addition salt by treatment with an appropriate acid, in particular oxalic acid, preferably in a solvent such as tetrahydrofuran.
If it is desired to isolate the isothiourea (IV) this is also preferably isolated in the form of a stable salt, e.g. the bis-maleate, by treatment with an appropriate acid, preferably in a solvent such as tetrahydrofuran.
The compound of formula (Ill) in which R1 is CH2CH2L where L is halogen (e.g. chlorine) and in which R2 is a hydrogen atom may be prepared by reacting a compound of formula (VI)
(in which L' is a leaving group e.g. methylthio) with a haloalkylamine such as chloroethylamine preferably in the form of a salt e.g. a hydrochloride. The reaction is carried out in a suitable solvent such as water, in the presence of a base such as triethylamine, and preferably at an elevated temperature, for example at about 1000C.
The compound of formula (III) where R1R2N is an ethyleneimino group may be prepared by reaction of ethyleneimine with a nitroethenamine of formula (VII)
where L" is a leaving group for example a C,~4 alkoxy group or a C14 alkylthio group, preferably methylthio. The reaction may be carried out in a suitable aprotic solvent such as acetonitrile.
The acid addition salts of the thiol of formula (II), the compound of formula (III) where R,R2N is an ethyeneimino group, i.e. the compound of the formula (VIII)
and the isothiourea of formula (IV) and acid addition salts thereof are all novel compounds and should be regarded as part of the present invention.
The thiol of formula (II) and the isothiourea of formula (ill) are not particularly stable but it has been found that they can be stabilised by converting then into the form of an acid addition salt.
Examples of such stable acid addition salts include hydrochlorides, sulphates, alkyl and aryl sulphonates, acetates, fumarates, maleates and benzoates. A preferred acid addition salt of the thiol of formula (II) is an oxalate, and a preferred acid addition salt of the iso;hiourea (IV) is the bis maleate.
The invention is illustrated by the following Examples.
Preparation 1 1 -[([5-[( Dimethylamino) methyl]-24uranyljmethyljthioi nmethanimidamide, maleate ( 1 :2) 5-[(Dimethylamino)methyl]-2-furanmetkonol (3.1 g) was added gradually to a solution of thiourea (1.53 g) in concentrated hydrochloric acid (5 ml). After standing at room temperature for 1 8h, the solution was heated at 98100 for :30 minutes. The solution was cooled, tetrahydrofuran (100 ml) and an excess of anhydrous sodiurn carbonate added and after 30 minutes the mixture was filtered.
A solution of maleic acid (4.65 g) in dry tetrnhydrofuren (40 ml) was added to the filtrate and the solid which separated was filtered, washed with tetrahyd.rofurnn and ether to give the title compound (8.1 g) m.p. 144-145c.
Preparation 2 5-[(Dimethylamino)methyl]-2-furanmethanethiol, oxalate (1:1) 5-[(Dimethylamino)methyl]-2-furanmethanol (7.76 g) was added gradually to a solution of thiourea (3.81 g) in concentrated hydrochloric acid (12.5 ml). After 18h, the solution was heated for 30 minutes at 98100 and evaporated to low bulk. A solution of sodium hydroxide (10 g) in water (50 ml) and sodium dithionite (10 g) was added and after 1 h the solution was extracted with ether (6x50 ml). Boric acid (35 g) was added to the aqueous fraction and the suspension was extracted with ether (4x 50 ml). To the combined ethereal extracts was added sodium dithionite (2 g) and an excess of anhydrous sodium carbonate.After 3h, the mixture was filtered into a solution of oxalic acid (6.3 g) in dry tetrahydrofuran (60 ml).
The solid which separated was filtered, washed with tetrahydrofuran and dried to give the title compound (5.84 g), m.p. 1 16.5--1 180.
Preparation 3 N-(2-Chloroethyl)-N-methyl-2-nitro-l .l-ethenediamine To a solution of N-methyl-(1-methylthio)-2-nitroethenamine (5.93 g) and 2-chloroethanamine hydrochloride (18.56 g) in water (4 ml) at 98100 was added triethylamine (24 ml). The mixture was stirred at 98100 for 10 mins and a vacuum (12 to 20 mm.) applied for 50 mins. Water (8 ml) was added and the mixture heated in vacuo at 981000 for 20 mins. Acetone (200 ml) and an excess of anhydrous magnesium sulphate were added to the residue and the suspension refluxed for 45 mins.
The solid was filtered off and washed with hot acetone (3x50 ml). The combined filtrate and washings were cooled and the resulting crystalline precipitate separated by filtration. The filtrate was concentrated to 100 ml, the solid which separated was filtered off, and the filtrate evaporated to low bulk and chromatographed (silica/acetone). The appropriate eluate was evaporated in vacuo, the residue suspended in ethyl acetate:ether, 1:4 and filtered to give the title compound (2.8 g) m.p. 113- 1150..
T.l.c. silica; 2-butanone; RfO.4.
Preparation 4 NMethyl--(nitromethylene)-i -aziridine-methanarnine A solution of ethyleneimine (0.47 Q) and N-methyl-(1-methylthio)-2-nitroetheneamine (1.48 g) in acetonitrile (5 ml) was stirred at room temperature for 2 days. The suspension was evaporated in vacuo at room temperature and the residue extracted with hot ethyl acetate (100 ml). Evaporation of the extract in vacuo gave a residue which was suspended in ethyl acetate (50 ml) and filtered. The filtrate was evaporated to ca. 5 ml and chromatographed (silica/ethyl acetate). The appropriate eluate [TLC (silica/ethyl acetate) Rf 0.28] was evaporated in vacuo to give the title compound (0.33 g), m.p.
118119 .
Preparation 5 5[(Dimethylamino) methylj-24urnnrnethanethiol oxalate (1:1) A mixture of potassium carbonate (83.5 g), sodium metabisulphite (22.9 g) and 1 1 -[[[5-[(dimethylamino)methylj-24uranyUmethyl]thiojmethanimidamide maleate (1:2) (26.73 g) in water (140 ml) and ether (160 ml) was stirred under a nitrogen atmosphere at room temperature for 24h.
Anhydrous sodium carbonate (1 0 g) was added and after stirring for a further 2h, the ether fraction was separated and washed with a solution of sodium metabisulphite (5 g) and potassium carbonate (8 g) in water (60 ml). The ether extract was dried (Na2SO4) for 1 h and filtered into a solution of oxalic acid (7.6 g) in tetrahydrofuran (100 ml). The solid which separated (13.33 g) was crystallised from tetraiiydrofuran to give the title compound (12.20 g), m.p. 1 16.5--1 190.
Example 1 N-[2-[[5-[( Di methylamino) methyl]24uranylmethyl]thiojethyl]-N'-methyl-2-nitrn-1 1 - ethenediamine A mixture of N-(2-chloroethyl)-N'-methyl-2-nitro- 1,1 -ethenedia mine (0.9 g), 5 [(dimethylamino)methyl]-2-furanmethanethiol oxalate (1:1) (1.3 g) and potassium carbonate (2.7 g) in water (10 ml) and tetrahydrofuran (10 ml) was stirred under nitrogen at room temperature for 5 days.
The suspension was evaporated in vacua, the residue mixed with water (40 ml) and the suspension extracted with ether (2x30 ml). The aqueous fraction was evaporated in vacuo and the residue evaporated with ethanol (2 x 10 ml). Tetrahydrofuran (20 ml), MgSO4 and decolourising charcoal were added and after 1 hour the mixture was filtered. Evaporation of the filtrate gave an oil (1 g) which was chrornatographed (silica/methanol: 0.88 ammonia, 79:1). The appropriate eluate was evaporated and the oily reside (0.66 g) extracted with hot isopropyl acetate.The solid which separated was filtered to give the title compound (0.4 g), m.p. 65--680, which was not depressed on admixture with a sample prepared according to the method of Example 1 5 in British Patent Specification No: 1565966.
Example 2 N-[2-[[5-[(Dimethyla mino)methyl]-2-furanyl methyl]thio]ethyl]-N'-methyl-2-nitro-1,1 ethenediamine A mixture of 1 -[[[5-[(dimethylamino)methyl]-2-furanyl]methyljthioj methanimideamide maleate (1:2) (2.23 g), N-(2-chloroethyl)-N'-methyl-2-nitro-1,1-ethenediamine (0.9 g) and potassium carbonate (3.46 g) in water (10 ml) and tetrahydrofuran (10 ml) was stirred under nitrogen at room temperature for 5 days. The suspension was evaporated in vacuo; the residue suspended in water (50 ml) and extracted with ether (2x40 ml). The aqueous fraction was evaporated in vacuo and magnesium sulphate and tetrahydrofuran (100 ml) added.After 18 hours, the mixture was filtered and the filtrate evaporated to give a semi-solid which was chromatographed (silica/methanol). The appropriate eluate was evaporated in vacuo to give the title compound (0.3 g), which had an n.m.r.
identical to that of the product according to Example 1 above.
Example 3 N-[2-[[5-[(Dimethylamino) methyl]-2-furanyl-methyl]thio]ethyl]-N'-methyl-2-nitro-1,1 - ethenediamine To a mixture of 5-[(dimethylamino)methyl]-2-furanmethanethiol, oxalate (1 :1) (0.156 g), sodium dithionite (0.05 g) and anhydrous sodium carbonate (0.15 g) in water (0.4 ml) was added ether (1 5 ml) and an excess of anhydrous sodium carbonate. The mixture was filtered and the filtrate evaporated in vacuo. To the residue was added N- methyl-a-(nitromethylene)-1 -aziridinemethanamine (0.072 g) and methanol (2 ml) and the solution evaporated to dryness.The resiaue was heated at 98100 for 1.25 h and the product chromatographed (silica/methanol -0.88 ammonia, 79:1). The appropriate eluate was evaporated in vacuo to give the title compound (0.113 g), which had an n.m.r. identical to that of the product of the above Examples.
Example 4 N-[2-[[5-[(Di methylamino)methyl]-2-furanyl methyl]thio]ethyl]-n'methyl-2-nitro-l .1- ethenediamine To a stirred mixture of 5-[(dimethylamino) methyl]-2-furanmethane-thiol oxalate (1:1) (1.31 9) and N-(2-chloroethyl-N'-methyl-2-nitro-1 ,1-ethenediamine (1.08 g) in water (20 ml) at 450 under an atmosphere of nitrogen was added a solution of potassium hydroxide (1.04 g) in water (3 ml). The solution was stirred at 450 for 2.5 hr. and at room temperature for 15 hr. The solution was then evaporated in vacuo, the residue dissolved in water and a stream of air passed into the mixture for 1 5 mins. The mixture was extracted with ether (2 x 5 ml) and the aqueous fraction evaporated in vacuo.
To the residue was added tetrahydrofuran (70 ml), an excess of anhydrous sodium carbonate, and decolourising charcoal. After 1 hr. the mixture was filtered, the filtrate evaporated in vacuo and the oily residue dissolved in 4-methyl-pentan-2-one (8 ml). The solid which separated was filtered and washed with 4-methylpentan-2-one to give the title compound (0.72 9), m.p. 63--660, which was not depressed on admixture with a sample prepared according to the method of Example 1 5 in British Patent Specification No. 1 565966.
Example 5 N-[2-[[5-[(Dimethyla mino) methyl]-2-furanyl methyl]thio] ethyl]-N'-methyl-2-nitro-1 ,1 - ethenediamine To a stirred solution of 1-[[5-[(Dimethylamino)methyl]-2-furanylmethyl]thio]methanimidamide maleate (1:2) (2.23 g) and N-(2-chloroethyl)-N'-methyl-2-nitro-1 1 -ethenediamine (1.08 g) in water (20 ml) at 450 under an atmosphere of nitrogen was added a solution of potassium hydroxide (1.68 g) in water (3 ml). After 40 hr. at room temperature the solution was extracted with ether (2x50 ml) and the aqueous phase evaporated in vacuo. Tetrahydrofuran (70 ml), decolourising charcoal and an excess of anhydrous sodium carbonate were added to the residue and the mixture refluxed for 30 mins. After 3 hours the mixture was filtered and the filtrate evaporated in vacuo to give a semi-solid which was dissolved in a mixture of methanol and acetone and chromatographed (silica; methanol:acetone 1:1).
The appropriate eluate was evaporated in vacuo to give the title compound as an oil (0.37 g), a portion of which was crystallised from 4-methylpentan-2-one, m.p. 68-70, which was not depressed on admixture with a sample prepared according to the method of Example 1 5 in British Patent Specification No. 1 565966.

Claims (11)

Claims
1. A process for the preparation of the furan derivative of formula (I)
which comprises reacting a thiol of formula (II)
with an alkylating agent of formula (III)
where R1 is the group -CH2CH2L, in which L is a leaving group, and R2 is a hydrogen atom, or R1 and R2, together with the nitrogen atom to which they are attached form an ethyleneimino group.
2. A process as claimed in claim 1 in which R1 is the group -CH2CH2L and R2 is a hydrogen atom.
3. A process as claimed in claim 1 in which RrR2N is an ethyleneimino group.
4. A process as claimed in claim 1 or 2 in which L is a halogen atom.
5. A process as claimed in any of claims 1 to 4 in which the thiol of formula (II) is generated in situ from an acid addition salt.
6. A process as claimed in any of claims 1 to 4 in which the thiol of formula (II) is generated in situ under basic conditions from the isothiourea (IV) or a salt thereof
7. The thiol of formula (II)
in the form of a stable acid addition salt.
8. The ethyleneimino derivative of formula (VIII)
9. The isothiourea of formula (IV)
and stable acid addition salts thereof.
10. A process for the preparation of a furan derivative of formula (I) as defined in claim 1 substantially as described with particular reference to the Examples.
11. The furan derivative of formula (I) when prepared by a process as claimed in any of claims 1 to 6or 10.
GB8100477A 1980-01-08 1981-01-08 Process for the preparation of a furan derivative Expired GB2067991B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB8100477A GB2067991B (en) 1980-01-08 1981-01-08 Process for the preparation of a furan derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB8000580 1980-01-08
GB8100477A GB2067991B (en) 1980-01-08 1981-01-08 Process for the preparation of a furan derivative

Publications (2)

Publication Number Publication Date
GB2067991A true GB2067991A (en) 1981-08-05
GB2067991B GB2067991B (en) 1983-10-19

Family

ID=10510510

Family Applications (1)

Application Number Title Priority Date Filing Date
GB8100477A Expired GB2067991B (en) 1980-01-08 1981-01-08 Process for the preparation of a furan derivative

Country Status (5)

Country Link
JP (1) JPS56103171A (en)
KR (1) KR840002007B1 (en)
BE (1) BE886997A (en)
CH (1) CH654830A5 (en)
GB (1) GB2067991B (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0055626A1 (en) * 1980-12-30 1982-07-07 Glaxo Group Limited Process for the preparation of a furan derivative
EP0055625A1 (en) * 1980-12-30 1982-07-07 Glaxo Group Limited Process for the preparation of a furan derivative
EP0058492A1 (en) * 1981-02-03 1982-08-25 Glaxo Group Limited Nitrovinyl derivatives for use in therapy and pharmaceutical compositions containing them
EP0059082A1 (en) * 1981-02-20 1982-09-01 Glaxo Group Limited Process for the preparation of a furan derivative
US4514413A (en) * 1982-04-10 1985-04-30 Basf Aktiengesellschaft Gastric acid secretion inhibiting N-(imidazol-1-ylalkyl)thiourea derivatives
US5686588A (en) * 1995-08-16 1997-11-11 Yoo; Seo Hong Amine acid salt compounds and process for the production thereof

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU1384197A3 (en) * 1983-07-15 1988-03-23 Рихтер Гедеон Ведьесети Дьяр Рт (Инопредприятие) Method of producing 1-[2-(5-(dimethylaminomethyl)-2-(furylmethylthio)-ethyl)] amino-1-(methylamino)-2-nitroethylene or its hydrochloride and method of producing dehydrochloride 2-(2-aminoethyl)-thiomethyl-5-(dimethylaminomethyl) - furan or its monohydrochloride

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0055626A1 (en) * 1980-12-30 1982-07-07 Glaxo Group Limited Process for the preparation of a furan derivative
EP0055625A1 (en) * 1980-12-30 1982-07-07 Glaxo Group Limited Process for the preparation of a furan derivative
EP0058492A1 (en) * 1981-02-03 1982-08-25 Glaxo Group Limited Nitrovinyl derivatives for use in therapy and pharmaceutical compositions containing them
EP0059082A1 (en) * 1981-02-20 1982-09-01 Glaxo Group Limited Process for the preparation of a furan derivative
US4514413A (en) * 1982-04-10 1985-04-30 Basf Aktiengesellschaft Gastric acid secretion inhibiting N-(imidazol-1-ylalkyl)thiourea derivatives
US5686588A (en) * 1995-08-16 1997-11-11 Yoo; Seo Hong Amine acid salt compounds and process for the production thereof

Also Published As

Publication number Publication date
KR830005191A (en) 1983-08-03
KR840002007B1 (en) 1984-10-27
BE886997A (en) 1981-07-08
CH654830A5 (en) 1986-03-14
GB2067991B (en) 1983-10-19
JPH0224827B2 (en) 1990-05-30
JPS56103171A (en) 1981-08-18

Similar Documents

Publication Publication Date Title
GB2067991A (en) Process for the Preparation of a Furan Derivative
US4497961A (en) Process for the preparation of ranitidine
KR940010179B1 (en) Process for the preparation of nitroethene derivatives
EP0064869B1 (en) Process for the preparation of a furan derivative
US4460506A (en) Nitrovinyl aziridine derivative
KR850001934B1 (en) Process for the preparation of a furan derivative
CZ288652B6 (en) Process for preparing {gamma}-mercaptocarboxylic acid derivatives
FI80450C (en) FRAME FOR EXAMINATION OF N- [2 - // 5 - / (DIMETHYLAMINO) METHYL] -2-FURANYLMETHYL / -THIO / EECL / -N&#39;METHYL-2-NITRO-1,1-ETENDIAMINE.
FI84059C (en) FORM OF FRAMSTAELLNING AV N- / 2 - // 5 - / (DIMETHYLAMINO) METHYL / -2-FURANYLMETHYL / THIO / EECL / -N&#39;-METHYL-2-NITRO-1,1-ETENDIAMINE.
EP0299034B1 (en) Process for the preparation of compounds with antiulcer action
EP0055626B1 (en) Process for the preparation of a furan derivative
FI90419B (en) Process for the preparation of 1- 2- [5-dimethylaminomethyl-2- (furylmethylthio) ethyl] amino-1-methylamino-2-nitroethylene and its hydrochloride
US4777260A (en) Synthesis of nizatidine intermediate
EP0230127A1 (en) Synthesis of nizatidine
KR810001914B1 (en) Method for preparing amino alkyl furan derivative
KR810001915B1 (en) Process for preparing amino alkyl furan deriatives
GB2217713A (en) Preparation of ranitidine

Legal Events

Date Code Title Description
PCNP Patent ceased through non-payment of renewal fee

Effective date: 19940108