Patent GB-1475590-A (GB)
Title: Heterocyclic compounds
IPC: C07D211/74
Filed: 1974-07-29
Abstract: 1475590 New heterocyclic compounds SANDOZ Ltd 29 July 1974 [2 Aug 1973 21 Dec 1973] 33344/74 Heading C2C The invention comprises compounds of Formula I wherein R 1  is amino, or wherein each of R 3  and R 4  is independently alkyl of 1 to 4 carbon atoms, R 2  is alkyl of 1 to 4 carbon atoms or phenyl, R 8  is hydrogen or alkyl of 1 to 4 carbon atoms, and A is -(CH 2 ) n -, wherein n is an integer from 1 to 3, with the proviso that when R 1  is amino, R 2  is methyl or phenyl and R 8  is hydrogen, n is 2 or 3, or >N-CO-R 5 , wherein R 5  is alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, a -(CH 2 ) m -R 6  group, wherein m is an integer from 0 to 2, and R 6  is phenyl, or phenyl monosubstituted by fluorine, chlorine, bromine, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or alkylmereapto of 1 to 4 carbon atoms, or an -OR 7  group, wherein R 7  is alkyl of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms, phenylalkyl of 7 to 10 carbon atoms, phenylalkyl of 7 to 10 carbon atoms monosubstituted in the phenyl ring by chlorine, alkoxy of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; phenylalkenyl of 8 to 10 carbon atoms, or phenylalkenyl of 8 to 10 carbon atoms monosubstituted in the phenyl ring by chlorine, alkoxy of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms. They may be prepared by reacting a compound of Formula II where X is chlorine, bromine, mercapto, or -SR 9  where R 9  is benzyl or alkyl of 1 to 4 carbon atoms, with hydrazine to produce a compound of Formula Ia and optionally reacting the latter with a compound of formula R 3 -CO-R 4  to produce a compound of Formula Ib The compound of Formula IIb may be prepared by reacting a compound of Formula IIc with a compound of formula R 9 X<SP>II</SP> where X<SP>II</SP> is Cl or Br, in a polar organic soluent and in the presence of an acid binding agent. The compound of Formula IIc may be obtained by reacting a compound of Formula IId where X<SP>III</SP> is Cl or Br with thiourea or optionally with sodium sulphide. The compound of Formula IIe may be obtained by heating a compound of Formula Va with a suitable chlorinating or brominating agent of phosphorus oxychloride, phosphorus trichloride or pentachloride or phosphorus oxybromide. The compound of Formula IIf may be obtained by reacting a compound of Formula VI with a compound of formula R 5 -CO-Cl in an inert solvent in the presence of an acid binding agent. The compound of Formula VI may be obtained by treating a compound of Formula VIII  with a suitable chlorinating or brominating agent e.g. phosphorus oxychloride, phosphorus trichloride or pentachloride or phosphorus oxybromide. The compound of Formula VIII may be obtained by removing the -COOR 7 <SP>I</SP> group with an acid from a compound of Formula Vb where R 7 <SP>I</SP> is lower alkyl. The compound of Formula V where A<SP>I</SP> is a -(CH 2 ) n  group or an # N-COOR 7 <SP>I</SP> group may be obtained by cyclizing a compound of Formula IX where Alk is lower alkyl, in an inert solvent, in the prescence of at least an equivalent amount of glacial acetic acid with hydrazine hydrate or a salt of hydrazine, and oxidizing the resulting compound of Formula X, preferably with bromine  The compound of Formula IX may be obtained by reacting a compound of Formula XI with a secondary, preferably a cyclic amine such as pyrrolidine, morpholine or piperidine to obtain an enamine of Formula XII where Y is a tertiary amine group, adding a compound of formula to the enamine obtained above, heating the reaction mixture, and removing the enamine group from the resulting reaction product of Formula XIV  by treating with water.