Pyrido thiazolo pyrimidines

Pyrido[2,3-d]thiazolo[3,2-a]pyrimidines [CaNS-C Na-CsN].—Pyrido[2,3-d]thia- 

Pyrido[l,2-a]thiazolo[5,4-e]pyriiiiidines [CsNS-C4Na-C6N].—Condensation of the thiazole (118) with ammonium carbonate yields compound (119). The same 

Pyriniido[24-6]benzothiazole8 [CgNS-CiNj-Ce].—2-Aminobenzothiazole reacts with methyl propiolate in THF to give largely 2H-pyrimido[2,l-b]benzothiazol- 

Pyrimido[5,4-g]benzothlazoles [CgNS-CiNa-Ce].—The a-hydroxymethylene ketone (121) reacts with benzamidine to give 8-methyl-5,6-dihydro-2-phenylpyrimido-[5,4- ]benzothiazole (122).  

Thiazolo[2,3- ]qi]inazolines [CsNS-C Ng-Ce].— Annelation of a thiazole ring to the quinazoline ring system may be carried out by standard procedures. Ester (123) reacts normally with hydrazine or phenylmagnesium bromide, but undergoes a complex rearrangement with piperidine or iV-methylpiperazine.  

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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). 

The reaction of 2-aminothiazole and isopropylidene bis(methylthio)-methylenemalonate (459, R2 = R3 = SMe) or 1-methylthioalkylidenema-lonates (459, R2 = Me, Et, Ph R3 = SMe) in boiling ethanol for 2.5 hr or in dimethylformamide at 120-130°C for 4-5 hr, gave 2-substituted 5-oxo-5//-thiazolo[3,2-a]pyrimidine-6-carboxylates (462) in good yields (89S-317). Similarly, in boiling ethanol, 2-substituted 4-oxo-4//-pyrido[l,2-a]-pyrimidine-3-carboxylic acids (463) were obtained in 80-85% yields. When anilines were reacted with isopropylidene bis(methylthio)methy-lenemalonate (459, R2 = R3 = MeS), (methylthio)(arylamino)methylene-malonates (464) were obtained 61-88% yields. 

Reaction of l-(nitromethylene)perhydropyrido[l,2-c]pyrimidine with p-chlorobenzenesulfonyl azide in dioxane at 80°C gave the tricyclic 1-nitro-6,6a,7,8,9,10-hexahydro-5//-pyrido[l,2-c][l,2,3]thiazolo[l,5-a]pyrimidine [79JCS(P1)2361],... 

Other successful uses of triethyl orthoformate include formation of pteri-din-4-ones from 2-aminopyrazine-3-carboxamide (see 9) and its derivatives127,229 233 234 cis- and trans-4a,5,6,7,8,8a-hexahydroquinazolin-4-ones from the related 2-aminocyclohexanecarboxamides61,65 pyrido[2,3-d]pyri-midin-4-ones (see 3) from 2-aminopyridine-3-carboxamide235 thiazolo[5,4-d]pyrimidin-4-one (see 148) from 5-aminothiazole-4-carboxamide236 and purin-6-ones (see 19) from 4-aminoimidazole-5-carboxamide.232,237 Any partial acetylation of 7c-excessive products can be reversed by a final alkaline treatment.238... 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

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