IE47545B1

IE47545B1 - N-cyano-n'-alkynyl-n"-(2-mercaptoethyl)-guanidines

Info

Publication number: IE47545B1
Application number: IE2933/81A
Authority: IE
Original assignee: Bristol Myers Co
Priority date: 1977-06-03
Filing date: 1978-06-02
Publication date: 1984-04-18
Also published as: IE812932L; IE812933L; IE47544B1

Description

The present invention relates to certain N-cyano-N' alkynyl-N"-(2-mercaptoethyl)-guanidines which are intermediates useful in the preparation of certain N-cyano-N*[2-[(4-methyl-5-imidazolyl)methylthio] -ethyl] -N-alkynyl guanidines which are receptor blocking agents, which inhibit gastric acid secretion and which are useful in the treatment of ulcers.

Accordingly, the present invention provides a compound of the formula: NCN HSCH2CH2NHCNH —R‘ ,1 (III) wherein R^ is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms.

In a preferred embodiment, R^ of the compound of formula III is in which R is hydrogen or methyl? in another preferred embodiment R^ is -(CH2) C = CR in which n is an integer 4 " of from 1 to 6 and R is hydrogen or methyl? and in still another preferred embodiment R^ is —C— CSCE4 I ch3 in which R is hydrogen or methyl.

In a more preferred embodiment, R1 of the compound of Formula III is a 2-butyn-l-yl, 3-butyn-l-yl, 4-pentyn5 1-yl, 2-methyl-3-butyn-2-yl or 3-butyn-2-yl group.

The compounds of the present invention are intermediates in the preparation of compounds of the formula: XCH3 H NCN II 1 CH2 SCH2CH2NHCNH-R wherein R1 is a straight or branched chain alkynyl group 10 containing from 3 to 9 carbon atoms.

The compounds of Formula I are described and claimed in Patent Specification No. 47543.

The compounds of Formula I may be prepared by reacting a compound of the formula: II or an acid addition salt thereof, in which X is hydroxy or a leaving group with a compound of the formula: NCN Ί 1 HSCH2CH NHCNH-R iii • 47545 wherein R^ is as above defined.

This process is illustrated, by way of example, by the following reaction scheme: CH3 NCN II + HSCH2CH2NHCNHCH2C = CH 'Nz H ch2oh/h CH„ NCN 'CH2SCH2CH2NHCNHCH2C == CH The compounds of the present invention may be prepared by reacting a compound of the formula: p-sch2ch2nh2 IV wherein P is a mercapto protecting group with a compound of the formula: NCN II 1 RSCNHR wherein -SR is a leaving group, and thereafter removing the protecting group P from the resulting compound to produce the compound of the invention.

This process is illustrated by the scheme given below: 475 NCN II PSCH2CH2NH2+RSCNHCH2C = CH 1) Heat 2) Deprotect NCN ll HSCH2CH2NHCNHCH2C sCH The present invention will be further described with reference to the following Examples.

EXAMPLE 1 N-Cyano-N'-propargyl-N-(2-mercaptoethyl)guanidine N-Cyano-N1-propar gyl-S-methylisothiourea (A) A solution of dimethyl cyanodithioiminocarbonate (16.00 g, 0.109 mole) and propargylamine (6.03 g, 0.109 mole) in acetonitrile (320 ml) was stirred at reflux for 4 hours, and then at 25°C for 12 hours. The mixture was cooled and filtered to yield N-cyano-N1-propargyl-S-methyl isothiourea.

N-Cyano-N' -propargyl-N-(2-mercaptoethyl) guanidine (B) A mixture of 1.136 g (10 m moles) of cysteamine hydrochloride, 1.53 g (10 m moles) of the product of step (A) above, and 0.055 g of hydroquinone in 10 ml DMF was slightly warmed to dissolve the compounds therein. To this solution was added 10 ml of an aqueous sodium hydroxide and nitrogen was bubbled through the solution.

After standing at room temperature for 17 hours, the reaction mixture was evaporated to dryness to give a mixture of the title product and sodium chloride. The title product was extracted from this mixture with 10 ml ethanol.

EXAMPLE 2 N-Cyano-Ν'- (2 -butyn-l-yl,) -N - (2 -mercaptoethyl) -guanidine N-Cyano-N-(2-butyn-l-yl)-S-methylisothiourea (A) A solution of dimethyl cyanodithioiminocarbonate (10.00 g, 0.0684 mole) and 2-butyn-l-ylamine (4.73 g, 0.0684 mole) in acetonitrile (200 ml) was stirred at 25°C for 0.5 hour, and then at reflux for 2.5 hours. The mixture was cooled and filtered to yield N-cyano-N'-(2butyn-l-yl)-S-methylisothiourea.

N-Cyano-N' -(2-butyn-1-yl) -N - (2-mercaptoethyl) guanidine (B) The general procedure of Example 1 (B) was repeated except that the N-cyano-N1-pxopargyl-S-methylisothiourea utilized therein is replaced by an equimolar amount of N-cyano-N'-{2-butyn-l-yl)-S-methylisothiourea, and the title product is thereby produced.

EXAMPLE 3 N-Cyano-Ν'-(3-butyn-l-yl)-N-(2-mercaptoethyl)-guanidine The general procedures of Example 1 steps A and B are repeated except that the propargylamine utilized in step A thereof is replaced by an equimolar amount of 3- butyn-1-ylamine, and the title compound is thereby produced.

EXAMPLE 4 N-Cyano-Ν'-(4-pentyn-l-yl)-N-(2-mercaptoethyl)-guanidine The general procedures of Example 1 steps A and B are repeated except that the propargylamine utilized in step A thereof is replaced by an equimolar amount of 4- pentyn-l-ylamine, and the title compound is thereby produced. - 7 EXAMPLE 5 N-Cyano-N'-(2-methyl-3-butyn-2-yl)-N-(2-mercaptoethyl)guanidine The general procedures of Example 1 steps A and B are repeated except that the propargylamine utilized in step A thereof is replaced by an equimolar amount of 1,1dimethylpropargylamine, and the title compound is thereby produced.

EXAMPLE 6 N-Cyano-N'-(3-butyn-2-yl)-N-(2-mercaptoethyl) guanidine The general procedures of Example 1 steps A and B are repeated except that the propargylamine utilized in step A thereof is replaced by an equimolar amount of 1ine thyl-propargylamine, and the title compound is thereby produced.

Patent Specification No. 47544 describes and claims compounds of the formulae NCN II 1 RZS-CNH-RX 2 . wherein R is as above defined and R is C. alkyl, aryl, j.—y substituted aryl, aralkyl, -CH2CN, -CH2COOH or -C^COOR' wherein R' is c^_g lower alkyl.

Claims

1. CLAIMS:1. A compound of the general formula: NCN HSCH 2 CH 2 NHCNH-R wherein R 1 is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms.

2. . A compound as claimed in claim 1 wherein R^ is -CHCseCR CH_ wherein R is H or CH . 3 1

3. A compound as claimed xn claim 1 wherein R is -(CH ) C—CR^ 2 n wherein R is H or CH^ and n is an integer of from 1 to 6, inclusive.

4. A compound as claimed in claim 1 wherein R^ is CH 3 I 1 4 — C-CSCR CH„ 15 wherein R is H or CH^.

5. A compound as claimed in claim 2 or claim 3 . 4 . wherexn R is H.

6. A compound as claimed in claim 2 or claim 3 4 wherein R is CH^. 20

7. A process for the preparation of a compound as claimed in claim 1 which process comprises reacting a compound of the formula: P-SCH 2 CH 2 NH 2 IV wherein P is a mercapto protecting group with a compound of the formula: NCN II RSCNHR’ ,1 5 wherein SR is a leaving group, and thereafter removing the protecting group P from the resulting compound.

8. A process for preparing a compound as claimed in claim 1 substantially as hereinbefore described with reference to any one of the Examples.

9. 10 9. A compound as claimed in claim 1 whenever prepared by a process as claimed in claim 7 or claim 8.