Patent GB-912496-A (GB)
Title: Amides and process for their preparation
IPC: C07D213/73
Filed: 1961-03-02
Abstract: The invention comprises compounds of the formula <FORM:0912496/IV (b)/1> (wherein Z is one or more hydrogen atoms, or lower alkyl, amino or lower alkylamino groups; R1 and R2 are hydrogen or lower alkyl; and R3 is lower alkyl or lower alkoxy, the word "lower" referring to groups containing at most 4 carbon atoms) and their non-toxic acid-addition salts; and their preparation by condensing a compound of the formula <FORM:0912496/IV (b)/2> (hereinafter referred to as Py-CH(R1)-X) with a compound of the formula <FORM:0912496/IV (b)/3> (hereinafter referred to as B-CO-Y) wherein (1) X is -NHR2 and Y is halogen, hydroxyl, azido, phenylthio, p-nitrophenylthio, OR1, OCOOR1 or OCOR1 wherein R1 is a possibly hindered alkyl group, a 1-imidazolyl group, -OCH2CN or OC(=CH2)OR1 and wherein when Y is OH the reaction can be carried out with the dialkylchlorophosphite, pyrophosphite, dialkylchloroarsenite or carbodiimide derivative; or (2) X is halogen, a quaternary ammonium group or an alkyl or arylsulphonate group and Y is -NHR2 and the metal salt of the amide is used (optionally when X is halogen); or (3) X is a group of the structure <FORM:0912496/IV (b)/4> and Y is OH.  Examples are given. Acid halides B-CO-Hal are prepared from the acid and phosphorus oxychloride or other halogenating agents.  Acid azides B-CO-N3 are prepared from the acid and hydrazine to give the hydrazide B-CO-NHNH2 which is then treated with nitrous acid.  Acid anhydrides B-CO-O-CO-R1 are prepared from BCOOH and R1COCl.  Compounds B-CO-O-CO-OR1 are prepared from BCOOH and R1OCOCl.  Phosphorus p derivatives BCOOP(OC2H5)2 are prepared from BCOOH and (C2H5O)2BCl or (C2H5O)2POP(OC2H5)2.  Arsenic derivatives BCOOA5(OC2H5)2 are prepared from BCOOH and (C2H5O)2A5Cl.  Imidazole derivatives B-CO-(1-imidazolyl) are prepared from BCOOH and di-imidazolyl ketone. Cyanoesters BCOOCH2CN are prepared from the triethylammonium salt of the acid and chloroacetonitrile.  Pyridine derivatives Py-N(R2)-P(OC2H5)2 are prepared from Py-N(R2)-H and (C2H5O)PCl or (C2H5O)2POP(OC2H5)2; and Py-N(R2)-P=N-Py are prepared from Py-N(R2)H anl PCl3.  2-Amino - 3 - aminomethyl-6-methyl-pyridine hydrochloride is prepared by hydrogenation of 2 - amino - 6 - methyl-nicotinonitrile.  3-Aminomethyl - 2 - n - butylamino-6-methyl-pyridine hydrochloride, 4 - aminomethyl - 2 - methylpyridine dihydrochloride, 3-aminomethyl-2-methylamino-6-methyl-pyridine dihydrochloride and 2-amino-3-aminomethyl-pyridine dihydrochloride are prepared similarly.  5 - Amino - 3 - aminomethyl-4,6-dimethylpyridine dihydrochloride monohydrate is prepared by reduction of 2-chloro-4,6-dimethyl-5-nitro-nicotinonitrile.  2 - n - Butylamino-6-methyl-nicotinonitrile is prepared from 2 - chloro-6-methyl-nicotinonitrile and n-butylamine.  3-Aminomethyl - 6 - (methyl and ethyl)-pyridine dihydrochlorides are prepared by reduction of 2-chloro-6-(methyl and ethyl)-nicotinonitriles.  3 - Methylaminomethyl - pyridine dihydrochloride is prepared by reacting 3-amino-methylpyridine with tosyl chloride to give N - (3 - pyridylmethyl)-p-toluenesulphonamide, reacting this with dimethyl sulphate to give N - methyl - N - (3 - pyridylmethyl)-p-toluene-sulphonamide and hydrolysing this.