Pyrido-thieno-pyrimidines

FAAH). Pyrido-thieno-pyrimidines have been prepared and screened as potential Cdc7 kinase inhibitors, alkoxythiazoles as isoform-selective RARP Ugands, ben-zamide tetrahydro-4H-carbazole-4-one as novel inhibitors of Hsp90, and pyrroles and pyrazolones as novel inhibitors of Mycobacterium tuberculosis. " ... 

All pyridothienopyrimidines prepared by annulation of thieno[2,3-6]pyridines are derivatives of two regioisomeric structures, namely, 5//-Lhieno[2,3,4-c, < /]pyrido[4,3-(i] pyrimidine (80) or pyrido thieno - lpyrimidine (81). 

Cyclocondensation of 3-cyano-2-methylthio-4//-pyrido[l, 2-u]pyrimidin-4-ones and ethyl mercaptoacetate in boiling EtOH in the presence of NaOEt afforded 4//-pyrido[l,2-u]thieno[2,3-r/ pyrimidin-4-ones 210 (00HC571). 2-Methylthio-4-oxo-4//-pyrido[l,2-u]pyrimidine-3-carboxylates 211 and mercaptoacetates afforded tricyclic derivatives 212 (93MIP1). Cyclocondensation of 2-methylthio-4-oxo-4//-pyrido[l, 2-u]pyrimidin-3-car-bonitriles 213 with H2NNH2 H2O and with guanidine HCl afforded tricyclic derivatives 214 and 215, respectively (96FES781). 

A recently developed synthesis (Scheme 94) of pyrido[3, 2 4,5]-thieno[3,2-d]pyrimidines starts with the appropriate iminophosphorane 257, which affords with heterocumulenes the tricyclic pyrimidines 258a-c (94T6705). 

Cyclocondensation of ethyl 2-methylthio-4-oxo-4/f-pyrido[l,2-a]py-rimidine-3-carboxylate 459 and ethyl mercaptoacetate in acetonitrile in the presence of potassium carbonate at 60°C for 2 hours, then at room temperature for 16 hours gave pyrido[l,2-a]thieno[2,3-t/]pyrimidine-2-carboxylate 460 (88CP1232904). 

New syntheses of pyrido[2,3-f>]thieno[3,2-rf]-pyrimidine and -1,2,3-triazine have been achieved <02SC3493>. Intramolecular conversion of l-aryl-3,3-dialkyltriazenes into... 

A new approach to 4,5-dihydro-9//-pyrido[l,2-a]thieno(3,2-c]pyrimidine-4,9-di-ones 198 is based on 1,3-dipolar cycloaddition of the above-mentioned mesoionic compounds with dimethyl acetylenedicarboxylate (2001JCR(S)304). 

The Sonogashira products of halopyrimidines with pendant functional groups are good precursors for synthesizing condensed heteroaromatie compounds. Yamanaka s group prepared four different condensed heteroaromatics from further manipulations of such Sonogashira products. Those four condensed heteroaromatics are 5-oxo-7-pyrido[4,3-6/] pyrimidine 192 [94], furo[2,3-6/]pyrimidine 195 [95, 96], thieno[2,3-6/]pyrimidine 198 [95, 96], and pyrrolo[2,3-6/]pyrimidine 202 [97-100]. 

A multistep preparation of a thieno[3,2-e]-l,4-diazepin-2(3//)-one (285) has been accomplished, starting from the thienooxazinone 284 obtained from methyl 3-acetylaminothiophene-3-carboxylate (283) and phosphorus pentachloride.154 Similarly, 3-methylthieno[2,3-d]pyrimidin-4-(3//)-ones (288) were obtained in an exothermic reaction by heating methyl 2-acylamino-3-thiophenecarboxylates (286) with N,AT-dimethylphosphordiamidate (287) up to 250°C155 (Scheme 78). Ethyl 2-acylamino-3-pyridinecarboxylate (289) gave, on heating with excess amine hydrochloride and phosphorus pentoxide/iV,AP-dimethylcyclohexylamine, a series of pyrido[2,3-d]pyrim-idine-4(3if)-ones (290).156... 

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