6-Aminopyrimidines

C10H10N4O2S. White powder, which darkens on exposure to light m.p. 255-256 C. Prepared by condensing p-acet-amidobenzenesulphonyl chloride with 2-aminopyrimidine and subsequent hydrolysis. Soluble sulphadiazine is the sodium salt. Sulphadiazine is the least toxic of the more potent sulphonamides. ... 

There is a scattered body of data in the literature on ordinary photochemical reactions in the pyrimidine and quinazoline series in most cases the mechanisms are unclear. For example, UV irradiation of 4-aminopyrimidine-5-carbonitrile (109 R=H) in methanolic hydrogen chloride gives the 2,6-dimethyl derivative (109 R = Me) in good yield the 5-aminomethyl analogue is made similarly (68T5861). Another random example is the irradiation of 4,6-diphenylpyrimidine 1-oxide in methanol to give 2-methoxy-4,6-diphenyl-pyrimidine, probably by addition of methanol to an intermediate oxaziridine (110) followed by dehydration (76JCS(P1)1202). 

Most pteridines are degraded to pyrazines and when they do yield pyrimidines, these may well be the ones from which they were made. However, some useful preparations of pyrimidines from pteridines are known. Thus, reduction of pteridin-7(8//)-one (732) and subsequent hydrolysis yields N-(4-aminopyrimidin-5-yl)glycine (733) (52JCS1620) and hydrolysis of 5,8-dimethylpteridine-6,7(5Ff,8Ff)-dione (734) gives dimethyl-... 

R = H) is made similarly from its ester (789 R = Et), itself prepared by several obvious steps (see (i) below) from the pyrimidine (788) which can be made by primary synthesis (66AP362). 4-Aminopyrimidine-5-carbonitrile (790 R = CN), which may be made by primary synthesis, undergoes hydrolysis in alkali to the amino acid (790 R = C02H) it may be made similarly from the amide (790 R = CONH2) (53JCS331). 

A major type of reaction in this class is the cyclization of 4-amino- or 4-halo-pyrimidines carrying 5-cyanoethyl or 5-ethoxycarbonylethyl groups, which cyclize to 7-amino or 7-oxo derivatives of 5,6-dihydropyrido[2,3- f]pyrimidine, e.g. (131)->(63). The intermediates may sometimes be prepared by reaction of 4(6)-aminopyrimidines with acrylonitrile, or even via a pyrimidine ring synthesis from an amidine and a cyanoacetic ester or malononitrile derivative, e.g. (132) -> (133) (7lJOC2 85, 72BCJ1127). 

The only example of this type which is noteworthy is the in situ cyclization to (156) of the intermediate (155) from a 5-aminopyrimidine anil and DMF dimethyl acetal (80S479). 

A rare type of reaction involves the photocyclization of the 5-(unsaturated acyl)aminopyrimidines (168) to reduced 7-methylpyrido[3,2-Similar reactions are known involving related 4-aminopyrimidine derivatives, leading to pyrido[2,3-[Pg.221]

There are two main classes here. Firstly, 5-substituted 4(6)-aminopyrimidines, e.g. the 5-ester (227), are reacted with esters in the presence of sodium (63CB1868), or with acetals in the presence of alkoxide (78KGS1549), to give pyrido[2,3-Keto esters give 6-ketones (229) (80USP4215216), whilst use of aminopyrimidine nitriles gives 7-oxo-5-amino derivatives (81USP4245094). 

Finally, 4-aminopyrimidine-5-carbaldehydes with cyclic jS-diketones, such as cyclo-hexane-l,3-dione, give partially reduced pyrimido[4,5-f>]quinolones (239) (76JOC1058). 

The only other pyrimidine-based preparation of pyrido[3,2-d]pyrimidines involves reaction of 5-aminopyrimidine with crotonaldehyde to give (255) (70JHC1219). 

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