Patent GB-1059719-A (GB)
Title: New sulphanilamide derivatives and process for their preparation
IPC: C07D239/69
Filed: 1965-10-14
Abstract: Novel sulphanilamide derivatives of the Formula I, and salts thereof with organic or inorganic bases, wherein R1 and R2 are hydrogen, halogen or a C1- 4 alkyl, alkoxy or alkylthio group or a cyclopropyl radical and R3 is hydrogen or a cyclopropyl radical, one only of R1, R2 and R3 being always a cyclopropyl radical, are made by reacting a compound of the Formula II with a compound of the Formula III, wherein either X is an amino group or an N-containing group convertible to an amino group by reduction or hydrolysis, Y is the group -NHM wherein M is a monovalent cation, Z is a halogen atom or a cyanamino or nitroamino radical or, if R1 and R2 are not alkylthio radicals, an alkylsulphonyl radical having at most 4 carbon atoms; or X represents an N-containing group convertible to amino by reduction or hydrolysis, Y is halogen or a C1- 5 acyloxy radical and Z is an amino group, and if necessary converting X into an amino group. <FORM:1059719/C2/1> <FORM:1059719/C2/2> <FORM:1059719/C2/3> Products wherein R1 and/or R2 are halogen may, if desired, be reacted with a metal compound of an alkanol or an alkyl thiol to form alkoxy or alkylthio derivatives, or may be reduced to eliminate the halogen atoms.  Pyrimidine compounds of the Formula III wherein R2 is the cyclopropyl radical are made by condensing a b -oxo-cyclopropane propionic acid alkyl ester with a thiourea, alkylisothiourea, alkylisourea or an alkanoic amidine to give a 6-cyclopropyl-4-pyrimidol optionally bearing a 2-mercapto-, 2-alkylthio- or 2-alkoxy-substituent which may then be converted to the 4-halo and other derivatives.  Compounds of the Formula III wherein R1 is the cyclopropyl radical are made by reacting cyclopropane carboxamidine with an alkyl alkanoylacetate or alkyl malonate, reacting the resulting 2-cyclopropyl -pyrimidin-4-ol or pyrimidine-4,6-diol with POCl3 or SOCl2 and converting the resulting halides to alkoxy or alkylthio compounds by reaction with an alkali-metal derivative of an alkanol or alkanethiol, if desired. Compounds of the Formula III wherein R3 is a cyclopropyl radical are made by reacting a cyclopropylmalonic or 2 - cyclopropylalkanoylacetic ester with an alkanoic amidine, O-alkyl-isourea or S-alkyl-isothiourea to give a 2-alkyl-, 2 - alkoxy- or 2 - alkylthio - 5 - cyclopropyl-pyrimidine - 4 - ol or pyrimidine - 4,6 - diol, which is then converted to the halide by the action of POCl3 or SOCl2 and, if desired, treated with an alkali-metal derivative of an alkanol or alkane thiol to give the alkoxy or alkylthio derivatives.  If thiourea is used in place of the S-alkyl-isothiourea as a reactant, to give a 2-mercapto-pyrimidine product, the mercapto group may be alkylated or removed by hydrogenation, if desired.  Pharmaceutical preparations having antibacterial activity comprise the above sulphanilamides or their salts with organic or inorganic bases and at least one pharmaceutical carrier. The preparations may be in forms adapted to internal or external administration, e.g. tablets, dragees, suppositories, syrups, powders, ointments or capsules.