Pyrimidines aminopyrimidines

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). 

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). 

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

Three general approaches to the synthesis of pjTido[2,3-d]pyrimi-dines from pyrimidines are available, all of which utilize an appropriately substituted 4-aminopyrimidine. The pyridine ring may be formed by the addition of three (route i), or two (route ii) carbon atoms, or by the intramolecular cyclization of a propionyl derivative (route in). 

Tisler and his group published the first synthesis of the parent unsubstituted l,2,4-triazolo[l,5-c]pyrimidine 4 by transforming 4-aminopyrimidine 1... 

Finally, Katritzky et al.sii have measured first-order rate coefficients for deuteration of pyrimidines by deuterated sulphuric acid (Table 152), and all pD and —D0 values given in the Table refer, as in the earlier work, to a temperature of 20 °C. For 2-aminopyrimidine, reaction clearly occurs on the free base and comparison of the data with the earlier work on anilines and by making a number of assumptions, conjugate acid at higher acidities is apparent and this follows the previously established pattern. This work yielded a value of 0.55 for [Pg.236]

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