Patent GB-1289209-A (GB)
IPC: C07D409/04
Filed: 1970-10-08
Abstract: 1289209 Spirothioxanthenes MERCK PATENT GmbH 8 Oct 1970 [15 Nov 1969] 47849/70 Heading C2C Novel compounds of Formula I in which R<SP>1</SP> is H or an alkyl group with up to 6 carbon atoms, R<SP>2</SP> is H or an alkyl group with up to 3 carbon atoms, or R<SP>1</SP> and R<SP>2</SP>, together with the nitrogen atom to which they are attached, form a morpholine ring or a pyrrolidine, piperidine or piperazine ring which may, if desired, be substituted by a methyl or ethyl group, and R<SP>3</SP> and R<SP>4</SP> are H or Cl, or a physiologically acceptable acid addition salt or quaternary ammonium salt thereof, are prepared by one of the following methods: (a) reducing an enamine of formula in which the dashed line denotes an optional bond, (b) reacting a compound of Formula IV in which Y is Cl, Br, I, OH, or a reactively esterified OH group, and R<SP>3</SP> and R<SP>4</SP> have the meanings specified above, with a base of the formula, R<SP>1</SP>R<SP>2</SP>NH, in which R<SP>1</SP> and R<SP>2</SP> have the meanings specified above, or with a reactant that yields such a base, (c) reducing a compound of formula in which the dashed line in the cyclohexane ring represents a double bond that may, if desired, be present in this position in the compound of Formula II, X is =NOH, =NR<SP>1</SP>, (H,NR<SP>2</SP>Ac<SP>1</SP>) or (H,NR<SP>1</SP>Ac<SP>2</SP>) or another group which can be converted by reduction to the group NR<SP>1</SP>R<SP>2</SP>, Ac<SP>1</SP> is an acyl radical with up to 6 carbon atoms, Ac<SP>2</SP> is an acyl radical with up to 3 carbon atoms, and R<SP>1</SP> ,  R<SP>2</SP>, R<SP>3</SP> and R<SP>4</SP> have the meanings specified above, (d) an organometallic compound of Formula VI in which M is-Li or MgHal, Hal is Cl, Br or I, and R<SP>3</SP> and R<SP>4</SP> have the meanings specified above, with a hydroxylamine derivative of the formula, R<SP>1</SP>R<SP>2</SP>NA, in which A is an alkoxy group having 1 to 4 carbon atoms or Hal, (e) by hydrogenolysing, hydrolysing, alcoholysing or aminolysing a compound corresponding to Formula I and in which the amino group is present in a functionally modified form, in order to liberate the amino group, and (f) by reacting a compound of formula with a thioether-bridge forming reactant in order to obtain intramolecular cyclization and, in each case, the product obtained may be converted into a salt. 21 - Chloro - spiro[cyclohexane - 1,91 - thioxanthene] - 4 - one is obtained by oxidation of 2-chlorothioxanthene to the sulphoxide which is converted successively to 9,9 - bis - (2 - cyanoethyl - 2 - chlorothioxanthioxanthene sulphoxide, 9,9 - bis - (2 - cyanoethyl) - 2 - chlorothioxanthene, hydrolysed to the dipropionic acid, esterified to the dimethyl ester which is cyclized to give 2<SP>1</SP> - chloro - spiro[cyclohexane 1,9<SP>1</SP> - thioxanthene] - 4 - one - 3 carboxylic acid methylester which is decarboxylated. Pharmaceutical compositions in conventional forms for oral or parenteral administration and having central nervous system activity, circulation influencing activity and spasmolytic and/or anti-histamine activity, comprise an above novel compound and carriers or diluents.