GB800635A - New derivatives of phenthiazine and processes for their production - Google Patents

New derivatives of phenthiazine and processes for their production

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Publication number
GB800635A
GB800635A GB3167255A GB3167255A GB800635A GB 800635 A GB800635 A GB 800635A GB 3167255 A GB3167255 A GB 3167255A GB 3167255 A GB3167255 A GB 3167255A GB 800635 A GB800635 A GB 800635A
Authority
GB
United Kingdom
Prior art keywords
bis
phenthiazine
dimethylamino
propyl
mixture
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
GB3167255A
Inventor
Raymond Jacques Horclois
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
Priority to GB3167255A priority Critical patent/GB800635A/en
Publication of GB800635A publication Critical patent/GB800635A/en
Expired legal-status Critical Current

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Abstract

The invention comprises compounds of the formula: <FORM:0800635/IV (b)/1> and their salts and quaternary derivatives, wherein X represents a hydrogen or halogen atom or a lower alkyl, lower alkoxy or lower acyl group, A represents a trivalent aliphatic hydrocarbon chain containing three carbon atoms each of which is linked to a different nitrogen atom and the groups R are methyl or ethyl groups (the word "lower" meaning that the group in question contains not more than four carbon atoms). Such compounds are obtained by (a) reacting a phenthiazine (appropriately substituted by the radical X) with a bis-(dialkylamino) - halogenopropane, especially a 1 : 3-bis - (dialkylamino) - 2 - chloropropane, wherein the alkyl groups are methyl or ethyl groups, or an acid addition salt thereof; (b) condensation of dimethylamine or diethylamine with a phenthiazine derivative of the formula: <FORM:0800635/IV (b)/2> (wherein A1 either represents the hydrocarbon chain A or a group convertible into the chain A by reduction, Z represents the residue of a reactive ester, such as a halogen atom or a sulphonic or sulphuric ester residue, Z1 is either the same as Z or represents an -N(R)2 group) and, where A1 is other than A, reduction of the grouping A1 into the aliphatic chain A; (c) cyclisation, preferably in a solvent in the form of a substituted amide of a lower aliphatic acid (such as formamides or acetamides) in the presence of a condensing agent (e.g. alkali metal hydroxide or carbonate) and, if desired, in the presence of a catalyst such as copper powder, of a derivative of the formula: <FORM:0800635/IV (b)/3> (wherein Hal represents a halogen atom, A1 either represents the hydrocarbon chain A or a group convertible into A by reduction) and, where A1 is other than A, reduction of the grouping A1 into the aliphatic hydrocarbon chain A. In method (a) suitable condensing agents are alkali metals or derivatives thereof, such as a hydride, amide, hydroxide, alcoholate or metal alkyl or aryl. The condensation yields a mixture of isomers, containing as substituents in the 10-position the groups -CH2-CH(NR2) -CH2-N(R)2 and -CH[CH2-N(R)2]2 respectively, which can be separated by fractional crystallization of their dihydrochlorides. The products can be used therapeutically as their acid addition salts, such as hydrohalides or 8-chlorotheophyllinates or as quaternary ammonium salts. In examples: (1) phenthiazine and 1 : 3 - bis - (dimethylamino) - 2 - chloropropane are reacted in toluene in the presence of sodamide to give a mixture of 10-[2 : 3-bis-(dimethylamino) - 1 - propyl] - phenthiazine and a minor proportion of 10-[1 : 3-bis-(dimethylamino) - 2 - propyl] - phenthiazine; (2) similarly obtained is a mixture of 10-[2 : 3-bis-(diethylamino) - 1 - propyl] - phenthiazine and 10 - [1 : 3 - bis - (diethylamino) - 2 - propyl]-phenthiazine; (3) and (4) the mixed bases of examples (2) and (1) respectively are separated by fractional crystallization of their hydrochlorides; (5) 1-(10-phenthiazinyl)-2-chloro-3-dimethylaminopropane hydrochloride (from the reaction of thionyl chloride on 1-(10-phenthiazinyl) - 2 - hydroxy - 3 - dimethylaminopropane) is heated in a sealed tube with dimethylamine to give 10-[2 : 3-bis-(dimethylamino)-1-propyl]-phenthiazine. Similarly obtained is 3-acetyl - 10 - [2 : 3 - bis - (dimethylamino) - 1-propyl]-phenthiazine, characterized as its neutral fumarate; (6) 3-methoxyphenthiazine and 1 : 3 - bis - (dimethylamino) - 2 - chloropropane are reacted in xylene in the presence of sodamide to give a mixture of 3-methoxy-10-[2 : 3-bis-(dimethylamino) - 1 - propyl) phenthiazine and a minor proportion of 3-methoxy-10-[1 : 3-bis-(dimethylamino) - 2 - propyl] phenthiazine. Similarly prepared are (7) a mixture of 3-methyl - 10 - [2 : 3 - bis (dimethylamino) - 1-propyl] phenthiazine and 3-methyl-10-[1 : 3-bis-(dimethylamino) - 2 - propyl] - phenthiazine; (8) a mixture of 3-chloro-10-[2 : 3-bis-(dimethylamino) - 1 - propyl] - phenthiazine and 3-chloro - 10 - [1 : 3 - bis - (dimethylamino) - 2-propyl]-phenthiazine; (9) a mixture of 1-chloro10 - [2 : 3 - bis - (dimethylamino) - 1 - propyl]-phenthiazine and 1 - chloro - 10 - [1 : 3 - bis-(dimethylamino) - 2 - propyl] phenthiazine. In further examples: (10) 10 - [2 : 3 - bis-(dimethylamino) - 1 - propyl] phenthiazine monoethiodide; and (11) 10-[2 : 3-bis (dimethylamino) - 1 - propyl] phenthiazine dimethiodide are prepared by quaternation of the base; (12) 10 - [2 : 3 - bis - (dimethylamino) 1 - propyl]-phenthiazine is prepared by refluxing a mixture of 21 - [2 : 3 - bis - (dimethylamino) propyl] amino - 2 - bromodiphenyl sulphide, dimethylformamide, potassium carbonate and copper powder. 21 - [2 : 3 - bis - (Dimethylamino) propyl] amino - 2 - bromodiphenyl sulphide is prepared by reacting 2-bromo-21-aminodiphenyl sulphide and 1 : 3-bis-(dimethylamino) 2-chloropropane in xylene in the presence of sodamide.
GB3167255A 1954-11-09 1954-11-09 New derivatives of phenthiazine and processes for their production Expired GB800635A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB3167255A GB800635A (en) 1954-11-09 1954-11-09 New derivatives of phenthiazine and processes for their production

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB3167255A GB800635A (en) 1954-11-09 1954-11-09 New derivatives of phenthiazine and processes for their production

Publications (1)

Publication Number Publication Date
GB800635A true GB800635A (en) 1958-08-27

Family

ID=10326679

Family Applications (1)

Application Number Title Priority Date Filing Date
GB3167255A Expired GB800635A (en) 1954-11-09 1954-11-09 New derivatives of phenthiazine and processes for their production

Country Status (1)

Country Link
GB (1) GB800635A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3130194A (en) * 1958-04-24 1964-04-21 Rhone Poulenc Sa Phenthiazine derivatives

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3130194A (en) * 1958-04-24 1964-04-21 Rhone Poulenc Sa Phenthiazine derivatives

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