Patent GB-808049-A (GB)
Title: Phenothiazine derivatives
Inventor: HORLEIN ULRICH
IPC: C07D417/06
Filed: 1956-08-30
Abstract: The invention comprises acyl phenthiazines of the general formula <FORM:0808049/IV (b)/1> (Ac is a straight or branched chain alkyl acyl radical containing from 2-4 carbon atoms, or an aryl acyl radical, e.g. benzoyl, X and Y are hydrogen atoms, alkyl radicals of up to eight carbon atoms, or halogen atoms, A is a straight or branched chain alkylene radical containing up to eight carbon atoms, and R1 and R2 are alkyl groups or straight or branched alkylene chains which are linked either inter se or with a carbon atom of A to form a 5- or 6-membered nitrogen containing ring, such as piperidine, pyrrolidine, morpholine or piperazine, which may be substituted by an alkyl group), quaternary compounds thereof, and processes for their preparation (a) by converting the corresponding 10-unsubstituted phenthiazine (or a derivative in which the carbonyl group is protected, e.g. by acetal or Schiff-base formation) into its metal compound by treatment with e.g. sodamide, potassamide, sodium or potassium hydroxide, or lithium phenyl, and then reacting it with a reactive ester of a basic alcohol HO.A.NR1R2; alternatively a reactive ester of an alcohol containing a group convertible into an amino group, e.g. a hydroxyl, halo, protected amino, or carbonamide group, may be used, with subsequent conversion to said group; (b) by heating a basic acylphenthiazine-10-carboxylic acid ester of formula <FORM:0808049/IV (b)/2> to between 140 DEG  and 220 DEG  C.  In examples: (1) 3-acetylphenthiazine and sodamide are refluxed in toluene and then g -dimethylaminopropyl chloride added, giving after further heating and removal of the solvent, 3-acetyl-10-(g -dimethyl-aminopropyl)-phenthiazine, characterized as its maleate and naphthalene - 1,5 - disulphonate; similarly (2) to (16) and (19) to (24) are prepared the following phenthiazines: 3-propionyl-10-(g  - dimethylaminopropyl) -, 3 - acetyl - 10-(b  - diethylaminoethyl), 3 - propionyl - 10 - (b -dimethylaminoethyl), 3 - propionyl - 10 - (b -dimethylaminopropyl) -, 3 - butyryl - 10 - (g -dimethylaminopropyl), 3 - benzoyl - 10 - (g  - dimethylaminopropyl), 3 - propionyl - 10 - (b  - N1-methyl - N11 - piperazinylethyl) -, 3 - acetyl-10 - (N1 - methylpiperidyl - 41 - methyl), 3 - propionyl - 10 - (N1 - methylpiperidyl - 41 - methyl), 3 - propionyl - 10 - (g  - N1 - piperidylpropyl), 3-propionyl - 10 - (b  - diethylaminoethyl), 3-butyryl - 10 - (b  - dimethylaminopropyl), 3-propionyl - 10 - (2 - [N - methyl - 21 - piperidyl] ethyl), 3 - methyl - 6 - propionyl - 10 - (g  - dimethylaminopropyl), 1 - methyl - 3 - or 6 - propionyl - 10 - (g  - dimethylaminopropyl), 3-chloro - 6 - propionyl - 10 - (g  - dimethylaminopropyl), 3 - chloro - 6 - acetyl - 10 - (g  - dimethyl-aminopropyl), 3 - methyl - 6 - acetyl - 10 - (g -dimethylaminopropyl), and 1 - methyl - 3 - or 6 - acetyl - 10 - (g - dimethylaminopropyl) phenthiazine, and in some cases their maleate, naphthalene-1,5-disulphonate, oxalate, or hydrochloride salts; (17) g -dimethylaminopropyl 3 - acetylphenthiazine - 10 - carboxylate is decarboxylated at 180-200 DEG  C. under vacuum giving 3 - acetyl - 10 - (g  - dimethylaminopropyl) phenthiazine; (18) the corresponding 3-propionyl compound is similarly obtained; (25) to (27), quaternary derivatives of the products of (17) and (18) are prepared by reaction with dimethyl sulphate and with benzyl chloride.  3 - Propionyl -, 3 - butyryl -, 3 - benzoyl -, 3-methyl - 6 - propionyl - and 1 - methyl - 3 or 6-propionyl-phenthiazines are prepared by methods analogous to that for 3-acetylphenthiazine. Specification 808,050 is referred to.