Thiazolo- pyrimidine

Cyclacel described thiazolo-pyrimidine analogs, exemplified by 104 [268, 269], and a related series of 2-aminophenyl-4-phenylpyrimidines, exemplified by 105a,b [270] with activity against PLK-1. These compounds were derived... 

S.F. McDonald and A.P. Mahadevan Studies in the Azole Series. Part XII. Some Thiazolo-pyrimidines. J. chem. Soc. 1949, 1064. 

The reaction of dimethyl acetylenedicarboxylate with the thiazolo-pyrimidine 1-oxide (183) resulted in the formation of the pyrimidothiazine (184). The latter compound underwent thermal ring-contraction to the pyrrolopyrimidine (185) (Scheme 85). ... 

Abdel-Hafez reported the synthesis of fused thiazolo-pyriniidines 104 (Y = NH2, OH) and thiazolo-pyrimidines 105 (R = CN, COOEt) (Scheme 46) by refluxing 103 with active methylene derivatives e.g., diethylmalonate (X = COOEt) or ethyl cyanoacetate (X = CN), or with some aiylidine malonitriles (benzylidinemalononitrile (R = CN and ethylbenzylidinecyano-acetate (R = COOEt)) [71],... 

Among other condensed thiazole ring systems, imidazo[2,l-6]thiazoles (tetramisole is a member of this class), thiazolo-pyrimidines, and thiazolo-pyridines continue to attract the most interest. Attention is concentrated on synthesis and biological activity. Unexpectedly, dihydrothiazolo[3,2-a]pyridinium bromide is readily brominated when the pyridine ring has a 3-nitro-substituent but not when it has a 3-amino-substituent. 

Reaction of 2-aminothiazole with ethyl acrylate yields 5.6-dihydro-7H-thiazolo[3,2a]pyrimidin-7-one (116) (Scheme 78) (169). 

Condensation of 2-phenyl-4-amino-5-benzoylthiazole with urea yields thiazolo[4.5-d]pyrimidines 127 (Scheme 84) (49). 

Treatment of 2-imino-3-phenyl-4-amino-(5-amido)-4-thiazoline with isocyanates or isothiocyanates yields the expected product (139) resulting from attack of the exocyclic nitrogen on the electrophilic center (276). Since 139 may be acetylated to thiazolo[4,5-d]pyrimidine-7-ones or 7-thiones (140). this reaction provides a route to condensed he erocycles (Scheme 92). 

Refluxing, 5.6-dihydro-7H-thiazolo[3,2-a]pyrimidine-7-one (370j with isopropylamine led to 2-imino-3-[2-(isopropylaminocarbonyl)ethyl]-thiazoline (371) (108). Similarly. tetrahydrobenzothiazolo[3,2-fl][2.3-f>]-quinazoline is opened by potassium hydroxide, yielding 373 (Scheme 214)... 

This kind of nucleophilic reaction, when performed with 7H-thiazolo[3,2-a]pyrimidine-7-one (374), however, is reported to give 2-[(/3-aminoacryloyl)imino]-4-thiazoline (375) (Scheme 215) (273, 703),... 

Heating 5-amino-4-mercapto pyrimidines (61) with formic acid affords the corresponding thiazolo[5,4d]pyrimidines (62) (Scheme 28) (357, 382, 411, 431). 

Amongst the more unusual reactions, 2,3-thiazolo fused pyrido[3,2-d]pyrimidines have been prepared from 3-aminopicolinic acid and 2-bromothiazoles, whilst a similar derivative resulted with allyl isothiocyanate (221 222) <72IJC602). Similar products are also produced in [3 + 3] reactions of 2-aminothiazoles (Section 2.15.5.7.1). 

Other C—C fused systems are also available by utilization of 1,4-dicarbonyl-type systems. The substituted pyrimidinethione (59) on treatment with polyphosphoric acid readily formed the thiazolo[5,4-d]pyrimidine system (60) without any of the alternative ring closure product (65JOC1916). 

Thiazolo[3,2-c]pyrimidinium, anhydro-8-ethoxy-2,3-dihydro-5-methyl- H NMR, 6, 676 (69ACS2437) 5H-Thiazolo[3,2-a]pyrimidin-5-one IR, 6. 681 (71JCS(C)2094)... 

Thiazolo[5,4-d]pyrimidine, 2,5,7-trichloro-nucleopfulic substitution, 6, 686 Thiazolo[3,2-a]pyrimidine-5,7-diones IR spectra, 6, 672 Thiazolopyrimidines synthesis, 5, 572, 574, 578 Thiazolopyrimidines, amino-purine synthesis from, 5, 591 Thi azolo[3,2-ajpyrimidines synthesis... 

Thiochrome (2,7-dimethyl-5//-thiachromine-8-ethanol 3,8-dimethyl-2-hydroxyethyl-5//-thiazolo[2,3 l, 2 ]pyrimido[4, 5 -d]pyrimidine [92-35-3] M 262.3, m 227-228 , pK st 5.8 (thiazol-N protonation). Crystd from chloroform. 

A mixture of 2 g of 4,5-diamino-6-mercaptopyrimidine and 10 ml of 9B% formic acid was heated at 70°C for two hours and then evaporated to dryness on the steam bath to give as a residue, 7-amino-thiazolo (5,4-d) pyrimidine. 

To B20 mg of 7-amino-thiazolo (5,4-d) pyrimidine was added 2.5 cc of 2 N sodium hydroxide. The water was removed under reduced pressure. The sodium salt was then heated at 240°C for one hour, during which time it melted, gave off water and resolidified. The sodium salt of 6-mercaptopurine was dissolved in 15 ml of water and acidified to pH 5 with acetic acid. Yellow crystals of 6-mercaptopurine hydrate precipitated, according to U.S. Patent 2,933,49B. 

Imidazolopyrimidine 212, formed by reaction of 210 with bromoacetaldehyde 211, undergoes cyclization catalyzed by sulfuric acid to form the five-membered ring of l-phenyl-lH-pyrazolo[3,4-<7]thiazolo[3,2-tf]pyrimidin-4-one 213 in virtually quantitative yield (Scheme 14) <1996BML59>. 

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