6-Methylthieno pyrimidine

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). 

Several 4-amino-2-methylthieno[2,3-synthesized directly by heating o-aminocarbonitriles 48 in a methanolic solution of acetamidine hydrochloride containing sodium ethoxide (83CPB1177). By an indirect route, 4-amino-2-substituted methyl-5,6-dihydrothieno[2,3-c/]-... 

A direct approach to 3-aryl-2-chloro-4-iminothieno[2,3-d]pyrimidines 65a from A-aryl isocyanide dichlorides and o-aminocarbonitriles 48 was devised by Shishoo and Jain (92JHC883). 3-Aryl-4-imino-2-methylthieno [2,3-rf]pyrimidines 65b were obtained by heating a mixture of 2-acetyl-aminothiophene-3-carbonitriles 64a, phosphorus pentoxide, a primary ary-lamine hydrochloride, and /V,7V-dimethylcyclohexylamine hydrochloride in a molar ratio 1 6 4 4, at 160°C (88CS195 91EUP452002). Following similar reaction conditions but adding 8 parts of water to this reaction mixture... 

When 5-acetylpyrimidine-4(3//)-thiones 101 are cyclocondensed with a-halogeno compounds, 5-methylthieno[2,3-d]pyrimidines 102 are obtained. The isolation of 5-alkyl intermediates in these synthesis was sometimes unpredictable. 

When 2-methylthieno[2,3-d]pyrimidin-4-ones 159a were heated with aromatic aldehydes at 180°C in the presence of zinc chloride, the 4-oxo-2-(2-arylvinyl)thieno[2,3-d]pyrimidines 159b were formed (85GEP225993). 2-(2-Arylvinyl)-6-acetylthieno[2,3-d]pyrimidines 160a reacted with aromatic aldehydes in the presence of sodium hydroxide to yield the condensation product 160b (89PHA348). 

Dechlorination of 4-chloro-6-methylthieno[2,3-d]pyrimidine 164 with zinc in ethanol and acetic acid at 80°C gave compound 165. The latter was subjected to the Reissert reaction using two equivalents each of tributyltin cyanide and acyl chloride in dichloromethane at room temperature. With benzoyl chloride the mono-Reissert adduct 166 was obtained, whereas with acetyl chloride the di-Reissert product 167 (86JHC545). 

With tributyltin cyanide in the presence of benzoyl chloride or acetyl chloride, 6-methylthieno[2,3-d]pyrimidine gave the mono- or di-Reissert aducts 81 and 82, respectively (86JHC545). 

Condensation of 2-methylthieno [3,2-d]pyrimidines with furfural in acetic anhydride gave the 2-furylvinyl derivatives 117 [72GEP(O)2039662, 72GEP(O)2039663],... 

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... 

Acetoxydihydrotheaspirane 53 4-(2-Butylidene-3,5,5-trimethyl)- 2-cyclohexen-l-one 101 5,7-Dihydro-2-methylthieno[3,4-[Pg.1056]

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