Thieno pyrimidine-4 -thiones

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>. 

Aminothiophene-3-thiocarboxamide 41 was converted into the thieno[2,3-d]pyrimidine-4-(3/7)-thione 42 by heating in a mixture of acetic anhydride and triethyl orthoformate. 

Heating the o-aminocarbonitrile 48 (R2 = Ph, R3 = Ac) and triethyl orthoformate yielded the corresponding imine 56, which was treated with an alcoholic solution of sodium hydrogen sulfide to afford thieno[2,3-d]-pyrimidine-4(3H)-thione 69a (88JPR585). 

A large number of 5-unsubstituted thieno[2,3-d]pyrimidines 100 were obtained by reacting 5-formylpyrimidine-4(3//)-thiones 99 with the appropriate a-halogeno compound (ethyl bromoacetate, phenacyl bromide, chloroacetonitrile or chloroacetamide) in aqueous sodium carbonate at 50°C (93JHC1065). 

Russian workers (82KGS118) reported the synthesis of 5,6-dihydro-thieno[2,3-d]pyrimidine 122 by brominating 5-allylpyrimidine-4(3//)-thione 121. 

Deamination of 3-amino derivative 23 with sodium nitrile in acetic acid gave 5,6-dimethylthieno[2,3-d]pyrimidin-4(3//)-one [85IJC(B)432]. Using the same reaction procedure, 3-amino derivative 82b (R = NH2) was converted into the thieno[2,3-d]pyrimidine-2(l//)-thione 78b (90JHC269). 

Thieno[3,2-d]pyrimidine-2(l//)-thiones 217-219 and -4(3//-thiones 245 were S-methylated smoothly with methyl iodide in base to the corresponding 2-methylthio (82EUP43054 89CPB1197) and 4-methylthio (86JHC 1757) compounds. 5-Alkylation of thieno[3,2-d]pyrimidin-4(3//)-one-2(l//)-thione 223 with alkyl halides in dilute sodium hydroxide solution afforded 2-alkylthio derivatives 284. Nucleophilic displacement of the alkyl-thio group in compound 284 by primary amines has also been reported (90EUP404356). 

Heating compound 299 with phosphorus pentasulfide in a mixture of dioxane and pyridine gave 7-(2,3,5-tri-0-benzoyI-/3-D-ribofuranosyl) thieno[3,4-d]pyrimidin-4(3//)-thione 374, in 49% yield. Thione 375, obtained by debenzoylating compound 374, was converted into the 4-methyl-thio-7-/3-D-ribofuranosylthieno[3,4-d]pyrimidine 376 by reaction with excess methyl iodide in 0.1 N aqueous sodium hydroxide. Substitution of the... 

Dimethyl-3-phenyl-4-oxothieno[2,3-d]pyrimidine-2-thione (319) reacts with ethyl a-chlorophenylacetate in the presence of anhydrous potassium carbonate in boiling dimethylformamide (DMF)-acteone for 12 hr to give 6,7-dimethyl-2,9-diphenyl-9a-ethoxy-9-oxothiazolo[3,2-fl]thieno [2,3-d]pyrimidin-3(2//)-one (321) in 90% yield [81IJC(B)538] (Scheme 75). The absorption at 1745 cm (five-membered lactam C=0) in addition to that at 1690 cm (six-membered C=0) in the product supports the cyclic structure 321. The formation of 321 must have been through the initially formed unstable mesoionic compound 320, which adds 1 mol of ethanol, liberated during reaction, to afford 321. 

Condensation of 17 with thiourea gave the corresponding 4-imino-thieno[2,3-d]pyrimidine-2(l/7)-thiones 32 (92PS93 93PHA347). With PhCONCS, however, the 3-benzoyl-4-imino derivative 32 (R = COPh) (92PS93) or the 4-amino derivatives 33 (R - H) [89AP227 91EGP-(D)287503] were obtained. 

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