2-Amino-6-methyl pyrimidine

The first procedure involved starting with the methyl ketone 996, formation of the enamino ketone 997, and condensation with substituted guanidine derivatives to give the desired products 998, with substituent variation on the pyrimidine amino group. 

Pteridine synthesis from pyrazine precursors are usually applied in such cases where the formation of special derivatives cannot be achieved easily by the pyrimidine approach. Methyl 3-amino-2-pyrazinecarboxylate (362) reacts with thiophosgene to give the corresponding 3-isothiocyanato derivative (363) which cyclizes with primary amines, arylalkylamines, aminoalcohols, amino acids,... 

In Section 1.2 a it was mentioned that 2-methyl-4-amino-5-(amino-methyl) pyrimidine (XII, R=CH3) reacts with carbon disulfide, in the presence of (z-halo ketones to form 3-(2-methyl-4-amino-5-pyrimidinyl-methyl)-4-hydroxy thiazolidine-2-thiones (CXCV) rather than 1,2,3,4-tetrahydropyrimidino[4,5-a]pyrimidine-2-thione (XIII) [Table2f (method G)]. 

The same transformations occur with 2-methyl-4-hydroxy-5-(amino-methyl) pyrimidines. These special substituents on the thiazole ring have been studied especially in connection with vitamin and its analogs. 

Amino-2-methyl-5-pyrimidin-yl-methyl)-2-(l-ethoxycarbonyl- 1-hydroxy-ethyl) -5- (2-hydr-oxy-e.thyl)-4-methyl-l, 3-thiazoliumchlorid Hydrochloride 85% Schmp. 224-226°... 

Pyrimidines bearing amino groups adjacent to a carboxylic acid152,203,204 or carboxylic acid derivatives 1 10,205 208 have been used in the synthesis of pyrimido[5,4-r/]pyrimidines. Thus, methyl 2,5,6-triaminopyrimidine-4-carboxylate (1) on heating with benzamidine at 100 C furnishes 6,8-diamino-2-phenylpyrimido[5,4- f]pyrimidin-4-ol (2).110... 

Nimustine hydrochloride [systematic name 4-amino-5-(([N-(2-chloroethyl)-N-nitrosocarbamoyl]amino(methyl)-2-methyl pyrimidin-l-ium chloride] is... 

A plausible mechanism for the reaction is shown in Scheme 11.2. The carbonyl group undergoes two a-amino-methylation reactions on the same a-carbon of the ketone 12, which is catalyzed by L-proline through enamine catalysis. The cyclocondensation of the resulting substituted amines 19 with formaldehyde affords the desired spiro[indoline-3, 5 -pyrimidin]-2-one and spiro[indene-2,5 -pyrimidin]-l (3H)-one (Scheme 11.2). 

The pathways for thiamine biosynthesis have been elucidated only partiy. Thiamine pyrophosphate is made universally from the precursors 4-amino-5-hydroxymethyl-2-methylpytimidinepyrophosphate [841-01-0] (47) and 4-methyl-5-(2-hydroxyethyl)thiazolephosphate [3269-79-2] (48), but there appear to be different pathways ia the eadier steps. In bacteria, the early steps of the pyrimidine biosynthesis are same as those of purine nucleotide biosynthesis, 5-Aminoimidazole ribotide [41535-66-4] (AIR) (49) appears to be the sole and last common iatermediate ultimately the elements are suppHed by glycine, formate, and ribose. AIR is rearranged in a complex manner to the pyrimidine by an as-yet undetermined mechanism. In yeasts, the pathway to the pyrimidine is less well understood and maybe different (74—83) (Fig. 9). 

Other pyrimidine starting materials include 5-amino-6-methyl derivatives, which with oxalates give 6,7-dihydroxypyrido[3,2-acid derivatives, which with malononitrile are converted into 5,6-dihydro-7-aminopyrido[2,3-[Pg.227]

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