Patent GB-606714-A (GB)
Title: Process for the production of 2-(aminoalkyl) pyrimidines and derivatives thereof
IPC: C07D239/26
Filed: 1945-11-21
Abstract: 2-(Acylaminoalkyl)-pyrimidines, which may carry substituents R1, R2 and R3 (as defined below) in the 4-, 5- and 6-positions, are manufactured by reacting an amidine of the general formula <FORM:0606714/IV(b)/1> wherein n is an integer and X represents the residue of an organic carboxylic or sulphonic acid, with a substance which, in one tautomeric form, has the general formula <FORM:0606714/IV(b)/2> wherein R1 represents hydrogen or an alkyl, aryl or aralkyl group, R2 hydrogen, halogen or an alkyl or nitro group and R3 hydrogen or an alkyl, aryl, aralkyl or alkoxy group (e.g. acetylacetone, n - hexane - 2:4 - dione, 3 - methyl - n - pentane-2:4-dione, malonodialdehyde, nitro-, bromo- or chloro-malonodialdehyde, formylacetic ester, ethyl acetoacetate or ethyl propionacetate), or with a substance readily convertible thereto such as the alkali metal derivatives thereof (e.g. sodio formylacetone), acetals of the aldehydes and ketones (e.g. acetylacetone diethylacetal or b -ethoxyacrolein acetal) or o-alkyl ethers of the enol forms of the 1 : 3-diketones (e.g. O-ethylacetylacetone).  The reaction is preferably carried out in solution in a lower alkanol (which may contain water), and with heating (e.g. under reflux), and, if desired, in the presence of an acid acceptor (e.g. an alkali or alkaline-earth metal carbonate or bicarbonate, an alkali metal alkoxide or a tertiary base such as pyridine), which in any event should be present in at least sufficient amount to liberate the amidine wholly from its salt when it is employed in that form.  The amidine starting materials may be prepared by the process of Specification 605,952 from the corresponding nitriles X.NH.(CnH2n).CN, in which X may represent any of the carboxylic acyl groups enumerated in the said Specification, or by a similar process (e.g. as described in Specification 519,136) from nitriles of the above formula in which X represents the residue of a sulphonic acid, e.g. an ethane-, n-butane-, benzene-, naphthalene-, toluene-, or phenyl-ethane - sulphonyl residue, or especially a benzenesulphonyl group containing as a p-substituent an amino, acylamido, alkylamino or dialkylamino group or a group or atom readily convertible to or replaceable by an amino group (e.g. an acetylamino, dimethylamino, nitro, nitroso, azo or hydrazo group or a halogen atom), or also a benzenesulphonyl group containing other substituents (e.g. alkyl, hydroxy or alkoxy groups) in the p- or any other position or positions.  When X represents a carboxylic acyl group, the product may be hydrolysed by means of a mineral acid or aqueous alkali to a 2-aminoalkylpyrimidine (which may then be reacylated, e.g. with a benzenesulphonyl halide, which may be substituted in the p-position by an amino, acylamido or cyano group or a group readily convertible into an amino group), whilst when X represents a benzenesulphonyl group substituted in the p-position by a carboxylic acylamido group, the latter may be hydrolysed with aqueous caustic alkali to yield a 2-(p-aminobenzenesulphonamidoalkyl) - pyrimidine.  The products are useful for pharmaceutical purposes and as dyestuff intermediates.  In examples: (1) benzamidoacetamidine hydrochloride is refluxed with acetylacetone in ethanol in the presence of potassium carbonate to produce 2-benzamidomethyl-4 : 6-dimethylpyrimidine, which is hydrolysed with dilute hydrochloric acid to give 2-aminomethyl-4 : 6-dimethylpyrimidine; (2) p-acetamidobenzenesulphonamidoacetamidine hydrochloride is heated with acetylacetone, sodium bicarbonate, water and pyridine, yielding 2-(p-acetamidobenzenesulphonamidomethyl) - 4 : 6 - dimethylpyrimidine, and, after hydrolysis with aqueous sodium hydroxide solution, 2-(p-aminobenzenesulphonamidomethyl)-4 : 6-dimethylpyrimidine.