1.3.4- Thiadiazolo pyrimidine-5 ones

Treatment of 5,7-diamino-l,3,4-thiadiazolo[3,2-n]pyrimidinium ehloride (25) with Vilsmeier reagent gave the 7-formamido-l,2,4-triazolo[l,5-c]pyrimidin-5-one (27) (90JHC851) (Seheme 42). Compound 27 has presumably been formed via rupture of the 1,3,4-thiadiazole ring of 25 and... 

Heating the 5-isocyano-l,3,4-thiadiazolo[3,2- ]pyrimidin-5-one 115 with 10% hydrochloric acid gave a mixture of the 5-imino-l,3,4-thiadiazolo[3,2- ]pyrimidin-7-one 116 (10%) and the l,2,4-triazolo[l,5-c]pyrimidine-5,7-dione 117 (35%) (91JHC489). Formation of 117 probably occurred through thiadiazole ring rupture of 116 and recyclizatioii with its imino function together with desulfurization (Scheme 43). 

When 7r-deficient thiadiazoles are fused to an azine, electrophilic substitution is possible only in the presence of strongly electron-donating substituents (74BCJ2813) (Scheme 56). Some [l,3,4]thiadiazolo[3,2-a]pyrimidin-5-ones were brominated next to the oxo group (90DOK743). 

Tsuji obtained two isomeric l,3,4-thiadiazolo[3,2-a]pyrimidino compounds by changing the pH (Scheme 13) <91JHC489>. Thus treatment of 2-amino-5-substituted-thiadiazoles (82) with ethyl cyanoacetate (83) in the presence of sodium methoxide gave the 2-substituted 5-imino-6//-[ 1,3,4]-thiadiazolo[3,2-a]pyrimidine-7-one (84). When the same reaction was carried out in the presence of P2O5 and CH3SO3H instead of sodium methoxide, 7-amino[l,3,4]thiadiazolo[3,2-a]pyrimidine-5-one... 

Reaction of the amino-1,3.4-thiadiazole 86 with a series of benzaldehydes gave the arylidene amines 87 which when treated with arylacetyl chlorides and triethylamine gave 5-substituted l,3,4-thiadiazolo[3,2-fc]pyrimidin-6-ones 88 in good yields (75-95%). The reaction was thought to proceed by a (4+2) cycloaddition reaction between 87 and the ketene which was produced in situ by the interaction of arylacetyl chlorides and triethylamine <99JCR(S)36>. 

Other claims are the isothiazolo[4,5-d][l,2,3]triazine-4-ones (170) for the treatment of gout and eschemia <86EUP274654>, the 3-aryl[l,2,5]thiadiazolo[3,4-d]pyrimidine-7-ones as antiallergics <90EUP349239>, 3-dialkylaminoethyl-l,2,3-triazolo[4,5-d]pyrimidine-5,7-diones as bronchodilators <88EUP272226>, and the 5-aryl-1,2,3-triazolo[4,5-d]pyrimidines as antihypertensives <88USP4923874>. 

The sulfur can be reductively removed by one of the many methods utilized for sulfur heterocycles. For the fused pyrimidine (703) zinc in acetic acid can be used (64JOC2135). In the 7-formylamino analogue (704), however, Raney nickel in aqueous ethanol was the best reagent for the reductive cyclization to form adenines (705) (78JOC960). It has been pointed out that nucleophilic substitution at C-7 in the [l,2,5]thiadiazolo[3,4-d]pyrimidine system easily takes place. This makes the compounds (704) readily available as key substances in this convenient approach to the synthesis of 9-substituted adenine derivatives. 

Refluxing ethyl 2-[(ethoxycarbonyl)iniino]-2//-[l, 2,4]thiadiazolo[2,3-a]pyridine-8-carboxylate in dilute aqueous sodium hydroxide produces 2-sulfanylpyrido[2,3-[Pg.136]

The addition of chlorothioformyl chloride to a-amino-N-heterocycles can clearly take place in the opposite sense, the sulfur atom appearing adjacent to the exocyclic nitrogen of the starting material. This occurs when 2-aminothiazole or 2-amino-A2-thiazoline react in ethanol-free chloroform, resulting in thiazolo[2,3-c]-l,2,4-thiadiazol-3-one (186) or its 5,6-dihydro analog. The structure of the latter has been confirmed by X-ray analysis. 2-Amino- (and 4-amino-2,6-dimethyl)pyrimidine similarly afford 1,2,4-thiadiazolo[4,3-a]pyrimidin-3-one (187, R = H, 34%) and 5,7-dimethyl-l,2,4-thiadiazolo[4,3-c]pyrimidin-3-one (39%), respectively. Possible mechanisms of the reactions have been discussed.164... 

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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