GB814512A - New phenthiazine derivatives and their preparation - Google Patents

New phenthiazine derivatives and their preparation

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Publication number
GB814512A
GB814512A GB22353/57A GB2235357A GB814512A GB 814512 A GB814512 A GB 814512A GB 22353/57 A GB22353/57 A GB 22353/57A GB 2235357 A GB2235357 A GB 2235357A GB 814512 A GB814512 A GB 814512A
Authority
GB
United Kingdom
Prior art keywords
phenothiazine
dimethylsulphamoyl
dimethylsulphamoylphenothiazine
methyl
condensing
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.)
Expired
Application number
GB22353/57A
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.)
Rhone Poulenc SA
Original Assignee
Rhone Poulenc SA
Societe des Usines Chimiques Rhone Poulenc SA
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 Rhone Poulenc SA, Societe des Usines Chimiques Rhone Poulenc SA filed Critical Rhone Poulenc SA
Publication of GB814512A publication Critical patent/GB814512A/en
Expired legal-status Critical Current

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  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

The invention comprises phenothiazine derivatives of the general formula <FORM:0814512/IV (b)/1> and their acid addition and quaternary ammonium salts (wherein X is S or SO; R1 and R2 are the same or different and either each is an alkyl group containing not more than five carbon atoms, or one of R1 and R2 is such an alkyl group and the other is hydrogen, or R1 and R2 with the adjacent nitrogen atom form a heterocyclic group; A is a straight or branched chain divalent aliphatic hydrocarbon group containing two to five carbon atoms, unsubstituted or substituted by <FORM:0814512/IV (b)/2> wherein B is a single bond or a methylene group, the nitrogen atoms of the phenothiazine nucleus and <FORM:0814512/IV (b)/3> being separated by at least two carbon atoms), and their preparation by the following processes: (1) reacting a 3-dimethylsulphamoylphenothiazine (II): <FORM:0814512/IV (b)/4> with the compound (III): <FORM:0814512/IV (b)/5> (wherein Y is the acid residue of a reactive ester, e.g. a halogen atom or a sulphuric or sulphonic ester residue) in the form of the base or of a salt thereof; (2) thermally decarboxylating above 100 DEG C. an aminoalkyl phenothiazine-10-carboxylate (IV): <FORM:0814512/IV (b)/6> (3) reacting an amine HNR1R2 with a reactive ester (V): <FORM:0814512/IV (b)/7> (4) alkylating the corresponding primary or secondary amines; (5) when X is a sulphur atom reducing, e.g. by catalytic hydrogenation, a phenothiazine (VI): <FORM:0814512/IV (b)/8> (wherein A1 is such that A1-CH2- represents A); (6) cyclizing a compound (VII): <FORM:0814512/IV (b)/9> (wherein one of R3 and R4 is hydrogen and the other is a dimethylsulphamoyl group, and Hal is a halogen atom) in the presence of a basic condensing agent; (7) when <FORM:0814512/IV (b)/100> is a 4-acyloxyalkylpiperazino group, acylating the corresponding 4-hydroxyalkylpiperazino derivatives; and (8) when X is SO, oxidizing the corresponding compounds in which X is sulphur. When the group -A- is an asymmetric branched chain, isomerization may take place during the reactions involved in methods (1) and (2) above, and when the chain A contains an asymmetric carbon atom the compounds (I) may exist in optically active forms. The phenothiazines of the invention are preferably employed in the form of acid addition salts or quaternary ammonium derivatives. Examples describe the preparation of the following compounds by the methods indicated: 3-dimethylsulphamoyl - 10 - (3 - dimethylamino - 2 - methylpropyl) phenothiazine (1) and (6), as its hydrochloride and picrate; 3-dimethylsulphamoyl - 10 - (3 - dimethylaminopropyl) phenothiazine (1), (4) and (5), as its acid oxalate and methanesulphonate; 3 - dimethylsulphamoyl - 10 - (3 - 41 - methyl - 11 - piperazinylpropyl) phenothiazine, (1) and (2), and its diacid fumarate; 3-dimethylsulphamoyl-10-(3-41 - ethyl - 11 - piperazinylpropyl) phenothiazine, (1); 3 - dimethylsulphamoyl - 10 - (2 - dimethylaminopropyl) phenothiazine, (1), as its hydrochloride; 3 - dimethylsulphamoyl - 10 - (3 - 11-pyrrolidinopropyl) - phenothiazine, (1), as its hydrochloride; 3 - dimethylsulphamoyl - 10 - (3-morpholinopropyl) phenothiazine, (1), as its oxalate; 3 - dimethylsulphamoyl - 10 - (3 - 41-methyl - 11 - piperazinyl - 2 - methylpropyl) phenothiazine, (1); 3-dimethylsulphamoyl-10-(3 - 41 - hydroxyethyl - 11 - piperazinylpropyl) phenothiazine, (3), as its dimethanesulphonate; 3 - dimethylsulphamoyl - 10 - (3 - methylaminopropyl) phenothiazine, (3), as its hydrochloride; 3 - dimethylsulphamoyl - 10 - [3 - (4 - 31 - hydroxypropyl - 1 - piperazinyl) propyl] phenothiazine, (3); 3-dimethylsulphamoyl-10 - (3 - 41 - acetoxyethyl - 11 - piperazinylpropyl) phenothiazine, (7), as its di-acid maleate; 3 - dimethylsulphamoyl - 10 - (2 : 3 - bis - dimethylaminopropyl) phenothiazine, (2), and 3 - dimethylsulphamoyl - 9 - oxy - 10 - (3 - 41-methyl - 11 - piperazinylpropyl) phenothiazine, (8), (two dimorphic forms). 3 - Dimethylsulphamoylphenothiazine is obtained by cyclizing 2-bromo-21-amino-41-dimethylsulphamoyldiphenyl sulphide, itself prepared by iron/acetic acid reduction of 2-bromo-21 - nitro - 41 - dimethylsulphamoyldiphenyl sulphide, obtained in turn by a Sandmeyer reaction on 2 - amino - 21 - nitro - 41 - dimethylsulphamoyldiphenyl sulphide. 3 - Dimethylsulphamoyl - 10 - (3 - toluene - p-sulphonyloxypropyl) phenothiazine is obtained by condensing p-toluenesulphonyl chloride in pyridine with 3 - dimethylsulphamoyl - 10 - (3-hydroxypropyl) phenothiazine, itself prepared by the acid hydrolysis of 3-dimethylsulphamoyl-10 - (3 - tetrahydropyranyloxypropyl) phenothiazine, obtained in turn by reacting 3-tetrahydropyranyloxy - 1 - chloropropane with 3-dimethylsulphamoylphenothiazine in the presence of sodamide. 3 - (4 - Methyl - 1 - piperazinyl) propyl 3 - dimethylsulphamoylphenothiazine - 10 - carboxylate (and its di-acid maleate) is obtained by condensing 3 - (4 - methyl - 1 - piperazinyl) propanol with 3 - dimethylsulphamoylphenothiazine - 10 - carbonyl chloride, prepared in turn by the action of phosgene on 3-dimethylsulphamoylphenothiazine. 1 : 3 - bis - Dimethylamino - 2 - propyl - 3 - dimethylsulphamoylphenothiazine - 10 - carboxylate (and its dihydrochloride) is obtained by condensing 1 : 3 - bis - dimethylamino - 2 - propanol with 3 - dimethylsulphamoylphenothiazine-10-carbonyl chloride. 2 - Bromo - 21 - (3 - dimethylamino - 2 - methylpropyl) amino - 41 - dimethylsulphamoyldiphenyl sulphide is prepared by condensing 3-dimethylamino - 2 - methyl - 1 - chloropropane with 2-bromo - 21 - amino - 41 - dimethylsulphamoyldiphenyl sulphide in the presence of sodamide. 3 - Dimethylsulphamoyl - 10 - (2 - cyanoethyl)-phenothiazine (prepared by condensing acrylonitrile with 3 - dimethylsulphamoyl - phenothiazine) is hydrogenated in ethanol in the presence of Raney nickel and ammonia to give 3-dimethylsulphamoyl - 10 - (3 - aminopropyl)-phenothiazine, purified via its oxalate. Specification 813,025 is referred to.
GB22353/57A 1956-08-01 1957-07-15 New phenthiazine derivatives and their preparation Expired GB814512A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR814512X 1956-08-01

Publications (1)

Publication Number Publication Date
GB814512A true GB814512A (en) 1959-06-03

Family

ID=9266748

Family Applications (1)

Application Number Title Priority Date Filing Date
GB22353/57A Expired GB814512A (en) 1956-08-01 1957-07-15 New phenthiazine derivatives and their preparation

Country Status (3)

Country Link
CY (1) CY240A (en)
GB (1) GB814512A (en)
MY (1) MY6300002A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4668671A (en) * 1985-04-26 1987-05-26 Smith Kline & French Laboratories Limited Tricyclic derivatives and pharmaceutical use

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4668671A (en) * 1985-04-26 1987-05-26 Smith Kline & French Laboratories Limited Tricyclic derivatives and pharmaceutical use

Also Published As

Publication number Publication date
MY6300002A (en) 1963-12-31
CY240A (en) 1962-03-20

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