Thieno pyrimidin-7 ones

Despite the extensive use of microwave-enhanced reactions in order to effect syntheses, very little has been explored in the synthesis of thieno[3,2-i pyrimidines. One example of this newer technology being applied to heterocyclic systems involves the conversion of the formamidine 479 into 480 when treated with an amine under high-temperature microwave conditions (Equation 180) <20040L1523>. 

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. " ... 

Thieno[2,3-d ]pyrimidin-4(3 H) -one, 3-methyl-synthesis, 4, 1017 Thieno[2,3-d ]pyrimidin-4-ones synthesis, 4, 1017, 1018, 1022 Thieno[2,3-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[2,3-6]pyrrole, N-benzyl- H NMR, 4, 1042 UV spectra, 4, 1044 Thieno[2,3-c]pyrrole, N-ethyl-UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 5-aryl-synthesis, 6, 1009 Thieno[3,2-6]pyrrole, N-benzyl- H NMR, 4, 1041, 1042 lithiation, 4, 1051 UV spectra, 4, 1044 Thieno[3,2-6]pyrrole, 2,3-dihydro-desulfurization, 6, 984 oxidation, 6, 981... 

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). 

Imidazo[l,2-c]thieno[3,2-e]pyrimidines were investigated as possible broncho dilatators. A facile microwave-assisted route for the synthesis of these tricyclic thieno derivatives was reported in quantitative yields via intermediate 4-chlorothieno[2,3-d]pyrimidines themselves synthesized under one-pot reaction conditions. The last step was performed for only 1 min... 

Zinc dust has been used to reduce a tetrazole of the tricyclic system 57 to generate the corresponding bicyclic 2-amino-3,5,6-trimethyl-3//-thieno[2,3- /]pyrimidin-4-one 58 (Equation 8) <2000MOL835>. 

Surprisingly, only one example of the synthesis of thieno[3,4-,7 pyrimidines has been described starting from a pyrimidine ring. In CHEC-II(1996) <1996CHEC-II(7)229>, substituted 5-cyanouracils, upon reaction with elemental sulfur, led to the formation of compounds in this class. Now the use of a 5-cyanopyrimidino-2-thione 419 under similar conditions (Equation 156) leads to the thienopyrimidine 420 <1997HC0151>. 

The examples above open up synthetic approaches that involve manipulating either the amino or carboalkoxy moieties. The following examples illustrate the variety of ways in which these transformations have been used to synthesize thieno[3,2-4 pyrimidines. Scheme 37 describes one such method in which an intermediate urea derivative 456 is formed from 455 by reaction with ethyl isothiocyanatoformate. Cyclization to 457 occurs upon heating in an ethanolic alkoxide medium <2003BML107>. 

Nielsen (81CS(18)135) prepared thieno[2,3-4]pyrimidin-4(3//)-ones in 43-90% yield by heating 2-acylaminothiophene-3-carboxylates (330) with phosphorus pentoxide, N,N -dimethylcyclohexylamine and an amine hydrochloride at 180 °C. By raising the temperature to 240 °C, thieno[2,3-4]pyrimidin-4-amines (331) were obtained in 27-34% yield (Scheme 92). Phenyl N,N -dimethylphosphorodiamidate [(MeNH)2P(0)OPh], a well-known reagent for the synthesis of 3-methyl-4-oxo-3,4-dihydroquinazolines (77S180), reacts with thiophene derivatives of type (330) to give 3-methylthieno[2,3-4]pyrimidin-4(3/f)-ones (78ACS(B)303). 

Oxo-4//-thieno[2,3-(/][l,3]oxazines (332), which are available from 2-aminothiophene-3-carboxylic acids by introduction of a one-carbon unit either from acetic anhydride or from ethyloxalyl chloride, react with amines to give thieno[2,3-d]pyrimidin-4(3/i)-ones (Scheme 94) (72JMC106,79JMC505). 

Electrophilic substitution reactions of thieno[3,2-cf pyridine occur at position 7 (equation 38). With dimethyl sulfate in an alkaline medium, thieno[3,2-cf pyrimidin-4-one (347) yields an N-methyl derivative. 

Dave and Shah have reported a Gould-Jacod type reaction for the microwave-assisted synthesis of thieno[3,2-e]pyrimido[ 1,2-c]pyrimidines via intermediate thieno[2,3-d ] pyrimidines (Scheme 3.46)73. A one-pot synthesis of pyrano [2,3-d]pyrimidines was also described by Kidwai and co-workers starting from thiobarbituric acids. The thio-barbituric acid intermediates were also prepared by microwave heating, using basic alumina as the solid support (Scheme 3.46)74. 

Strong heating of 2-substituted 5-propargylsulfanyl-3-aryl-3//-pyrimidin-4-ones, and their 5-allylsulfanyl derivatives, has been shown to lead to 2-substituted 3-aryl-6-methyl-3//-thieno[3,2-d]pyrimidin-4-ones and their 6,7-dihydro derivatives. The proposed mechanism in both cases is a [3,3]-sigmatropic thia-Claisen rearrangement followed by tautomerization and a 5-exodig or 5-exo-trig cyclization.38... 

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