Patent CA-1165328-A (CA)
Inventor: NAGANO MITSUO
IPC: C07D317/68
Filed: 1981-03-20
Granted: 1984-04-10
Abstract: ABSTRACT         Process for preparing compounds useful as  munoregulatory and antineoplastic agents wh1ch are amino-acid derivatives of formula:                                                      (I) wherein:-n is an integer from 1 to 5;            R1 is a hydrogen atom, an alkyl group, a haloalkyl group, a halogen atom, a mercapto group, an alkylmercapto group, a hydroxy group, an alkoxy group, an acyloxy group, a carboxyl group, an alkoxycarbonyl group, an amino group, an alkyl-substituted amino group, an aryl-substituted amino group, an acylamino group, a haloalkoxycarbonylamino group, an alkanesulphonyl group, a nitro group or a cyano group (and, when n is an integer from 2 to 5 the rad1cals R1 may be the same or different);            R2 and R3 may be the same or different and each is a hydrogen atom or an alkyl group;            R4 is a hydrogen atom, an alkyl group, a cyano group, cyanoalkyl group, a hydroxyalkyl group, an alkoxycarbonyl group, a carboxyl group, an aryl group, an aralkyl group, a mercaptoalkyl group, an alkylthioalkyl group, or a thioalkyl group (the free bond of the sulphur in sa1d thioalkyl group being joined to the sulphur ABSTRACT   of another moiety of the same formula); and A is a hydroxy group, an alkoxy group, an amino group, an alkyl-substituted amino group (optionally halogen- or carbomyl-substituted in the alkyl moiety), a hydrazino group, an alkyl-or aryl- substituted hydrazino group, a hydroxylamino group, an alkoxyamino group or an aralkyloxyamino group;   or a pharmaceutically acceptable salt thereof, which process comprises:-(a) Reacting a compound of formula:                           with a compound of formula:             (in which either:          Z is a halogen atom, G is the group:                ABSTRACT and C?C is CH--CH;   or:       Z is the group:                    G is a hydrogen atom, and C?C is C-C) in the presence of a base, to give a compound formula:                               IV     (wherein R1,R2,R3,R4 and n are defined above: and M1 is and alkyl group); (b) Optionally hydrolysing the product of step (a) to give a compound of formula:                                                     VI     ABSTRACT  wherein R1, R2, R3, R4 and n are as defined above);          (c) Optionally heating the product of step (b) where R4 represents a carboxy group, to give a compound of formula:                      XIII     wherein R1, R2, R3 and n are as defined above);   (d) Optional1y condensing the product of step (b) to give an oxazoione of formula:                                 JX   and reacting the oxazolone thus obtained with a compound of formula:      (where M2 has the same meaning as A defined above, other than hydroxy or alkoxy) to give a compound of formula:                                                         XI      (wherein R1,R2,R3,R4, n and M2 are as defined above); and (e)  When the product of any of steps (a)-(d) is an acid, optionally salifying the said product so as to obtained a pharmaceutically acceptable salt thereof.     twherein M2 has the same meaning as A def1ned at,ove, other than hydroxy or alkoxy) to give a ccmpound of formula.                     Xl l~here~n 8~, R2, R3, R4, n and M2 are as defined above); and te) hhen the product of any of steps ta) - (d) is an acid, optionally salifying the said product so as to obtain a pharmaceutically aoceDtable szlt thereof.