Pyrimidine, 2-amino-, reaction with

Flowers et al.164 reacted perfluoro-2-methyl-2-pentene with 2-aminopyri-dine or 2-amino-4-methylpyridine in tetrahydrofuran at room temperature to obtain the pyrido[1.2-u]pyrimidines (95). Reaction with 2-amino-6-methylpyridine yielded the 1,8-naphthyridine (96). 

Acyl(or cyano)pyrimidines substituted at the 4-position with chlorine, methoxy or methylsulf-anyl have also been used as intermediates in the preparation of pyrimido[4,5-rf]pyrimidines by reaction with guanidine, urea, or amidines.110114 139,140 Thus, 5-phenylpyrimido[4,5-<7]-pyrimidine-2,4,7-triamine (35) is obtained by reaction of 2-amino-4-methoxy-6-phenylpyrimi-dine-5-carbonitrile (34) with guanidine.114... 

The reaction involves an electrophilic attack into the 5-position of the pyrimidine ring and thus only those pyrimidines that are activated toward electrophilic substitution by the presence of electron-donating substituents at the 2- and 4-positions undergo cyclization. 2,4,6-Triaminopyrimidine, 6-aminouracil, 6-amino-2-thiouracil, 4-amino-2,4 dimercaptopyrimidine, 2,4-diaminopyrimidin-6(l/I)-one, and various 4-amino-vV-alkyl and aryl pyriinidones have all been converted into pyrido[2,3-[Pg.160]

The same amino compounds also underwent reactions with a series of 3-cyano-4-imino- and 3-cyano-4-oxo-piperidines to yield 4-amino-5,0,7,8-tetrahydropyrido[4,3-d]pyrimidines. . A tetra-hydropyTido[4,3-prepared from 4-amino-l-henzyl-3-cyano-d -piperidine (134) hy a simple one-step preparation. This method is of general application for the preparation of fused pyrimidines and previous papers in this field are listed by Taylor. ... 

Hydrolyses of aminopyridopyrimidines to the corresponding pyridopyrimidones by means of acid, base, and nitrous acid have been reported. 4-Amino compounds are stable to nitrous acid, but are much more labile than the 2-amino derivatives toward acid- or base-catalyzed hydrolysis. The aminochloro-pyrido[2,3-d]pyrimidine (160) has been converted into the 2,4-dianilino analog (161) by reaction with aniline." ... 

Alkylpyrimidines were obtained in 59-70% yield from higher 1-dimethyl-amino- and l-methoxyalk-l-en-3-ynes (R = Me, Et, -Pr) by their reaction with formamide (70ZOR2374). The exception was l-methoxy-5,5-dimethylhex-l-en-3-yne, from which the pyrimidine was obtained in 45% yield only, which is related to steiic hindrance for the attack at the acetylene bond. 

Reaction of 9-bromo-2-morphohno-4//-pyrido[l, 2-n]pyrimidin-4-ones with 4-vinylpyridine in DMF at 80 °C for 16 h in the presence of CS2CO3 and PdCbCdppf), and with amines and phenols in boiling THF for 20 h in the presence of KOr-Bu and PdCbCdppf) yielded 9-[2-(4-pyridyl)vinyl), 9-(substituted amino), and 9-aryloxy derivatives, respectively (01MIP9). 4-Hydroxyaniline gave a 9-(4-hydroxyphenyl)amino derivative. 

Reaction of 3-formyM/7-pyrido[ 1,2- ]pyrimidin-l-ones with hydroxylamine O-sulfonic acid at 5 °C, then 50 °C yielded 3-nitriles <2003T4113>. Treatment of 2-hydroxy-3-(dimethylamono)methyF4//-pyrido[l,2- ]pyrimidin-4-one with Mel, then with KCN gave the 3-cyanomethyl derivative <2004MI215>. A condensation product was obtained from 5-amino-l-ethyl-6-hydroxy-l,3-dihydrobenzimidazol-2-one and 3-lbrmyl-2-hydroxyA//-pyndo[ 1,2- ]pynmidin-l-one <2002W002/38549>. l-(2-Aminopyrimidin-4-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-ones were prepared from l-(2-methylthiopyrimidin l-yl)-8-phenyl-l,2,3,4-tetrahydro-6//-pyrido[l,2- ]pyrimidin-6-one by treatment with MCPBA, and then with aralkylamines <2005W005/070932>. 

Table 20 Ring closures to [1,2,4]triazolo[1,5-a]pyrimidines by reaction of 3-amino[1,2,4]triazoles with /3-oxo ketones, esters, nitriles, or malonic acid derivatives...

The reaction of 2-amino-l-methylimidazole hydrochloride and EMME by heating in boiling ethanol in the presence of excess triethylamine overnight gave imidazo[l,2-tf]pyrimidine-6-carboxylate (1115, R = H) in 47% yield [82IJC(B)1030]. The similar reaction with 5-nitro-2-amino-1-methyl-imidazole yielded only a condensation product (1114, R = N02), which... 

A similar degenerate ring transformation was observed when 4-amino-6-chloro-l-methylpyrazolo[3,4-(f]pyrimidine was treated with dilute alkali. In this reaction as well, the expected product, 4-amino-6,7-dihydro-6-oxo-l-methylpyrazolo[3,4-(f]pyrimidine, was not obtained, but rather a rearranged isomer, i.e., 6-amino-4,5-dihydro-4-oxo-l-methylpyrazolo-[3,4- f] pyrimidine. The formation of this compound takes place according to the same mechanism as that postulated for the formation of 86 (Scheme 11.39) (54JOC1570). 

---