Patent GB-1117082-A (GB)
Title: Process for the preparation of substituted n-cyclopropylethylene diamines
Inventor: BIEL JOHN H
IPC: A61K31/135
Filed: 1965-06-23
Abstract: <FORM:1117082/C2/1> <FORM:1117082/C2/2> <FORM:1117082/C2/3> <FORM:1117082/C2/4> <FORM:1117082/C2/5> <FORM:1117082/C2/6> <FORM:1117082/C2/7> The invention comprises compounds of the formula I, wherein R represents an alkynyl, furyl, pyridyl, pyrrolyl, naphthyl or optionally disubstituted phenyl radical (said substituents being, the same or different, chlorine, bromine, iodine or fluorine atoms or trifluoromethyl, C1- 8 alkyl, C1- 8 alkoxy, C1- 8 alkylthio, di-(C1- 8 alkyl) sulphamyl, phenyl, phenoxy, benzyl or when taken together methylenedioxy groups), n represents 0 or 1; R1 represents a hydrogen atom or a C1- 8 alkyl, C2- 8 alkenyl, C2- 8 alkynyl, or C3- 7 cycloalkyl radical R2 represents a hydrogen atom or a C1- 8 alkyl, C2- 8 alkenyl, C2- 8 alkynyl, phenyl-(C1- 4 alkyl) or phenyl-(C2- 4 alkenyl) radical; R3 represents a hydrogen atom or a C1- 8 alkyl, C2- 8 alkenyl, C2- 8 alkynyl, Ph, Ph-alk- or Ph-alken-radical (where Ph represents a disubstituted phenyl radical as defined above and -alk- and -alkenrepresent C1- 4 alkylene and C2- 4 alkenylene radicals respectively) and Y represents a C1- 8 alkylene, C2- 8 alkenylene, C2- 5 alkynylene, C1- 8 oxyalkylene or C1- 8 thioalkylene group and pharmaceutically acceptable non-toxic salts thereof and their preparation by reducing compounds of the formula XXVII or XXIX in an inert solvent with substantially 1 or more equivalent parts of a reducing agent capable of reducing a carbonyl group but not a triple bond, by reacting a compound of the formula I wherein at least one of R1, R1 and R2 represents a hydrogen atom and n represents O when R represents a hydrogen atom, in an inert organic solvent, with substantially one or more equivalent parts of a Grignard reagent and reacting the resultant product with substantially one or more equivalent parts of a reactive organic halide, reacting a compound of the formula A with a reactive compound of the formula R2X, where R2 has a value defined above other than hydrogen and X represents a halogen atom, in an inert organic solvent and in the presence of an acid acceptor or where R2 represents a methyl group, by reacting compounds of the formula A with formaldehyde and formic acid.  Glycinamides of the formula XXVII may be prepared by acylating a primary or secondary amine of the formula XXIV with an a -haloacetyl halide or a -tosylacetyl halide of the formula X-CH2-CO-Z, wherein X represents a halogen atom or a tosyl group and Z represents a halogen atom, in the presence of an acid acceptor and reacting the resulting cyclopropylacetamide of the formula XXVI with a primary or secondary amine in the presence of an acid acceptor.  Glycinamides of the formula XXIX may be prepared via haloacetamides of the formula XXVIII, according to method described above for the preparation of glycinamides of the formula XXVII. Therapeutic compositions with anti-depressive and mono-amine oxidase inhibiting properties, in forms suitable for oral or parenteral application, comprise compounds of the Formula I and their non-toxic addition salts together with a suitable carrier.