Patent GB-1277227-A (GB)
Title: Aryl esters
IPC: C07D213/89
Filed: 1969-10-03
Abstract: 1277227 Aryl esters of aminomethylcycliccarboxylic acids DAIICHI SEIYAKU CO Ltd 3 Oct 1969 [14 Oct 1968 12 Dec 1968] 48814/69 Heading C2C Novel compounds of formula Q-COO-Aryl wherein Q represents a trans-4-aminomethylcyclohexyl or 4 - aminomethyl - phenyl group and "Aryl" represents a phenyl, pyridyl, N- oxide-pyridyl or naphthyl group which is unsubstituted or has one or more substituents selected from hydroxy, halogen, nitro, amino, carboxyl, formyl, sulphamoyl, carboxyalkylamino having 1-6 carbon atoms, alkoxy having 1-6 carbon atoms, alkenyl having 1-6 carbon atoms, phenyl, carboxyalkoxy, carboxyalkenyl, carboxyalkylcarbonyl, hydroxyalkyl, alkoxycarbonyl and carboxyalkyl, the carboxyalkyl group being unsubstituted or substituted in the alkyl portion thereof by amino, hydroxy or halogen, and the pharmaceutically acceptable salts of said compounds are prepared by reacting a compound of formula Q<SP>1</SP>-CO-X wherein X is halogen and Q<SP>1</SP> is Q in which the amino group is blocked with a protective group such as is used in the field of peptide synthesis, with a compound of formula HO-(Aryl)<SP>1</SP> wherein (Aryl)<SP>1</SP> has any of the meanings specified above for "aryl" or differs only in that any amino group which may be present is protected with a benzyloxycarbonyl group and any hydroxy or carboxyl group which may be present is protected by a benzyl group and the HO- group is bonded directly to a carbon atom of the aromatic nucleus in (Aryl)<SP>1</SP>, and then removing any protective groups present. Intermediates of formula Q<SP>1</SP>-COO(Aryl)<SP>1</SP> prepared in the above reaction may be isolated before removal of protective groups and examples are 4<SP>1</SP>- benzyloxycarbonylphenyl trans-4- N-benzyloxycarbonylaminomethylcyclohexane- 1 - carboxylate, 4<SP>1</SP> - (2<SP>11 </SP>- benzyloxycarbonylvinyl)phenyl trans - 4 - N - benzyloxycarbonylaminomethylcyclohexane  -  1 - carboxylate, 21- nitro - 4<SP>1</SP> - methoxycarbonylphenyl trans - 4- N-benzyloxycarbonylaminomethylcyclohexane- 1 - carboxylate, 4<SP>1</SP> - N<SP>1</SP> - (2<SP>11</SP> - benzyloxycarbonylamino - 2<SP>11 </SP>- benzyloxycarbonylethyl)- phenyl trans - 4 - N - benzyloxycarbonylcyclohexane - 1 - carboxylate, 4<SP>1 </SP>- formylphenyl trans - 4 - N - benzyloxycarbonylcyclohexane- 1 - carboxylate which was also reduced with sodium borohydride to the corresponding 4<SP>1</SP>- hydroxymethylphenyl ester, 4<SP>1 </SP>- (1<SP>11</SP> - oxo- 5<SP>11</SP> - benzyloxycarbonyl - n - pentyl)phenyl trans - 4 - N - benzyloxycarbonylcyclohexane- 1 - carboxylate which was also reduced with sodium borohydride to the corresponding 1<SP>11</SP>- hydroxy compound, 4<SP>1 </SP>- (2<SP>11 </SP>- benzyloxycarbonylvinyl)phenyl trans - 4 - N - tertbutyloxycarbonyl - aminomethylcyclohexane- 1 - carboxylate, 4<SP>1</SP>- (2<SP>11</SP> - carboxyethyl)phenyl trans - 4 - N - benzyloxycarbonyl aminomethylcyclohexane - 1 - carboxylate, 4<SP>1</SP> - nitrophenyl and 4<SP>1 </SP>- methoxyphenyl 4 N - benzyloxycarbonylaminomethyl benzoates, 4<SP>1 </SP>- (2<SP>11</SP>- benzyloxycarbonylamino - 2<SP>11</SP> - benzyloxycarbonylethyl)phenyl 4 - N - benzyloxycarbonylaminomethylbenzoate, 41 - (2<SP>11 </SP>- benzyloxycarbonylvinyl)phenyl 4 - benzyloxycarbonylaminomethylbenzoate, 4<SP>1 </SP>- formylphenyl and 4<SP>1</SP> - hydroxymethylphenyl 4 - N - benzyloxycarbonylaminomethyl benzoates. trans - 4 - N - Benzylorycarbonylamino. methylcyclohexanoic acid chloride is prepared by reaction of the amino acid with benzyloxycarbonyl chloride and treated with SOCl 2  and trans - 4 - N - tert - Butyloxycarboxy 1 - aminomethylcyclohexanoic acid chloride is prepared similarly. Various phenols of formula (Aryl)<SP>1</SP>-OH used in preparing the above intermediates are prepared by protecting groups prior to reaction. Pharmaceutical compositions in conventional forms for oral and parenteral administration and having anti-plasmin, anti-trypsin and antikallikrein activity comprise an above novel compound and a carrier.