Patent GB-1478671-A (GB)
Title: N-(substituted phenyl) amidines and processes for their preparation
IPC: C07C275/70
Filed: 1974-06-17
Abstract: 1478671 N - (substituted phenyl) - amidines SCHERICO Ltd 17 June 1974 [20 June 1973] 26773/74 Heading C2C Novel compounds and their acid addition salts I in which M is [where R<SP>1</SP> is H, C 1-6  alkyl, C 3-6  cycloalkyl, OH, C 1-6  alkoxy, C 3-6  cycloalkoxy or phenyl (optionally substituted by NO 2 , CF 3  or Hal), R<SP>2</SP> is H, C 1-6  alkyl or C 3-6  cycloalkyl or R<SP>1</SP> and R<SP>2</SP> together are C 3-7  alkylene or -(CH 2 ) 2# (CH 2 ) 2 - (where #is >O, >S, >NH or >N C 1-6  alkyl) and R<SP>8</SP> is H or C 1-6  alkyl], X is N0 2 , CF 3 , Cl, Br or I, Y is H, Hal, NO 2 , amino optionally mono- or di-C 1-6  alkylated, C 1-6  alkyl, C 1-6  alkoxy, polyfluoro C 1-6  alkoxy, polyfluoro C 1-6  alkyl, polyfluoro C 1-6  alkylthio, NR<SP>3</SP>COR<SP>5</SP> or NR<SP>3</SP>SO 2 R<SP>4</SP> (where R<SP>3</SP> is H or C 1-6  alkyl, R<SP>4</SP> is C 1-6  alkyl, aralkyl or aryl and R<SP>5</SP> is C 1-6  alkoxy, aralkoxy, aryloxy, C 1-6  alkyl, aralkyl or aryl), R is a divalent alkane or alkene radical in which at least one C atom has more than two C atoms bonded to it and any double bond in the alkene moiety is not conjugated with the amidine group and Z is H, OH, C 1-6  alkoxy, aryl C 1-6  alkoxy, C 1-6  alkanoyloxy, aryl C 1-6  alkanoyloxy carbamoyloxy or thiocarbamoyloxy both optionally mono- or di-C 1-6 alkylated with the proviso that when X is Cl, Br or I at least one of R1, R<SP>2</SP>, R<SP>8</SP> or Z is other than H are prepared by (1) reacting a compound II in which A- is an anion, Q<SP>4</SP> is Hal or an alkoxy or aralkoxy radical and Z is as above other than hydroxy with an appropriate amine R<SP>1</SP>R<SP>2</SP>NH to form a compound I (Z # OH); (2) condensing an aniline IV or a reactive derivative thereof with an appropriate imidate or the corresponding free base, in which Q<SP>2</SP> is Hal, alkoxy or alkylthio to form a compound I (Z # OH); (3) condensing an amide or thioamide X=C(NR<SP>1</SP>R<SP>2</SP>)-R-Z (where X is O or S) with an appropriate amine VI or a reactive derivative thereof or an amide or thio amide VIII with an appropriate amine R<SP>1</SP>R<SP>2</SP>NH or reactive derivative thereof to produce a compound I (Z # OH); (4) the Beckmann rearrangement of a compound X in which T is an acyl radical in the presence of an amine R<SP>1</SP>R<SP>2</SP>NH to form a compound I [M = -N=C(NR<SP>1</SP>R<SP>2</SP>)-]; (5) reacting an amine VI or a salt thereof with a nitrile Z-R-CN optionally in the presence of compounds capable in a manner known per se of introducing groups R<SP>1</SP>a and R<SP>2</SP>a, where R<SP>1</SP>a is C 1-6  alkyl, C 3-6  cycloalkyl or phenyl (optionally substituted by NO 2 , CF 3  or Hal), R<SP>2</SP>a is C 1-6  alkyl or C 3-6  cycloalkyl or R<SP>1</SP>a and R<SP>2</SP>a are as defined for R<SP>1</SP> and R<SP>2</SP> together to form a compound I (R<SP>1</SP> = H or R<SP>1</SP>a, R<SP>2</SP> = H or R<SP>2</SP>a); (6) converting X=NH 2  to X=C1, Br or I using the Sendmeyer reaction in compounds I (Y is other than amino) ; (7) eliminating NH2 from a compound equivalent to a compound I. (except that Y is not amino) and containing such a group; (8) reducing a compound XV in which Q<SP>5</SP> is a double bond conjugated with the amidine double bond to form a compound I (R = alkylene; Z = H); (9) hydrolysing a compound XIX to form a compound I (Z = OH); (10) alkylating a compound I (M = to replace the N-hydrogen atom with C 1-6  alkyl ; (11) alkylating a compound I (R<SP>1</SP> = H, OH and/or R<SP>2</SP> = H) to give a compound I (B<SP>1</SP> = C 1-6  alkyl, C 3-6  cycloalkyl, C 1-6  alkoxy or C 3-6  cycloalkoxy and/or R2 = C 1-6  alkyl or C 1-6  cycloalkyl); (12) converting Y = NH 2  to mono- or di-C 1-6  alkylamino, halogen or NR<SP>3</SP>COR<SP>5</SP> (where R<SP>3</SP> is H or C 1-6  alkyl, R<SP>5</SP> is C 1-6  alkyl, aralkyl (or aryl) by methods known per se in compounds I; (13) hydrolysing Y = acylamino or reducing Y=NO 2  to NH 2  in compounds I; (14) subjecting a compound I (Z = C 1-6  alkoxy or aryl C 1-6  alkoxy) to ether cleavage to produce compounds I (Z = OH); (15) acylating or etherifying a compound I (Z=OH) to form a compound I (Z = C 1-6  alkoxy, aryl C 1-6  alkoxy- C 1-6  alkanoyloxy, aryl-C 1-6  alkanoyloxy or di- C 1-6  alkylcarbamoyloxy; (16) reducing an alkenyline group R to the corresponding alkylene group; or (17) forming a salt by salification of a compound I. Compounds I are anti-androgenic agents and form with a carrier or excipient a pharmaceutical or veterinary composition which may be administered orally, parenterally or rectally. They may also be admixed with animal feedstuff.