6//-Pyrido pyrimidine-6-thione

In aqueous alkaline conditions with chloroacetic acid the pyrido[4,3- f]pyrimidinethione (80) undergoes facile ring opening, attributed to the resonance stabilization of a delocalized covalent hydrate dianion intermediate (81) (82). Pyrido[2,3- f]pyrimidine-4-thiones (and... 

The thiones are readily desulfurized with Raney nickel to give the corresponding unsubstituted compounds in bicyclic systems in the 2-, 4- and 7-positions, and in tricyclic systems such as (95). The 2-methylthio derivatives may be similarly desulfurized. Thione groups in the 4-position, but not the 2-position, in pyrido-[2,3- f ]- and -[3,2- f]-pyrimidines may be replaced directly with ammonia or amines. 

Pyrido[2,3-d]pyrimidine-2-thione, 7-phenyl-reactions, 3, 211 Pyridopyrimidinethiones reactions, 3, 213 Pyrido[2,3-d]pyrimidinethiones reactions, 3, 213... 

Treatment of pyrimidine-2-thione 193 with AICI3 in PhN02 yielded 2-(4-benzylphenyl)-6-oxo-6,7-dihydro-4//-pyrido[6,l-a]isoquinolin-4-thione (194) (98MI47). Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquina-zoline-2,4-dione (195) in PPA afforded l,2,3,5,6,7-hexahydropyrimido[3,2, l-//]quinazoline-l,3,7-trione (196) (97CHE96). 

Treatment of resin-bound iminophosphorane 197 with an excess of solid CO2 and CS2 in a sealed glass tube, and with aryl isocyanates afforded I-OXO-, 1-thioxo- 198, and l-arylimino-l//-pyrido[l,2-c]pyrimidine-3-car-boxylates 199 (OlJMClOll). Reaction of iminophosphorane 200, derived from 2-(2-azidophenyl)pyridine with excess PPh3, yielded 6//-pyrido[l,2-c] quinazoline-6-thione (201). 

Reaction of 2-pyridineacetamides 197 with Me2NCH(OMe)2 afforded 3//-pyrido[l,2-f]pyrimidin-3-ones 198 (Equation 42) <1998WO98/027098, 2000USP6147080>. Reaction of l-(2-aminocthyl)-l, 2,3,4-tetrahydroisoquino-lincs with CS2, C(OEt>4, and nitroguanidine gave 1,2,3,6,7,1 1 h-hexahydro-4//-pyrimido[6,l -<2 isoquinoline-4-thiones, 4-ethoxy-1,6,7,1 lb-tetrahydro-2//-pyrimido[6,l -zz isoquinolines, and 4-(nitroimino)-l,2,3,6,7,l lb-hexahydro-... 

Reaction of 2-cyanomethylpyridine with iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)-iV -(4-methylphenyl)carbodiimides, and with (1,1,2,2,2-pentachloro- and l,l-dichloro-2,2,2-trifluoroethyl)isocyanates or A-methoxycarbonyl-l,2,2,2-tetrachloro-, — l-chloro-2,2-trifluoroacetaldehyde imines afforded 3-aryl-4-cyano-l-(4-methylphenyl)imino-3-trifluoromethyl-2,3-dihydro-17/-pyrido[l,2-f]pyrimidines and 4-cyano-3-trichloro-, 4-cyano-3-trifluoro-17/-pyrido[l,2-4pyrimidin-l-ones, respectively <2004CHE47>. Refluxing 2-cyanomethylpyridine and iV-(l-aryl-l-chloro-2,2,2-trifluoroethyl)isocyanates in benzene furnished l-aryl-4-cyano-l-trifluoromethyl-l,2-dihydro-3//-pyrido[l,2-4pyrimidin-3-ones. However, when the solution of the isocyanate was added dropwise to the solution of 2-cyanomethylpyridine, and the reaction mixture was then treated with NEt at room temperature, the isomeric 3-aryl-4-cyano-3-trifluoromethyl-2,3-dihydro-l//-pyr-ido[l,2-dpyrimidin-l-ones were obtained. Reaction of l-(acetyl- and benzoylmethylene)-6,7-dimethoxy-l,2,3,4-tetra-hydroisoquinolines with PhCONCS yielded 1-acetyl-, 1 -benzoyl-9,10-dime thoxy-3-pheny 1-6,7-dihydro-2//-pyrimido[6,l- ]isoquinoline-2-thiones <2003SL2369>. 

The treatment of Ar-(2-pyridinyl)acylacetamides 56 with P4SI0 gave 4-substituted 2//-pyrido[l,2-a]pyrimidine-2-thiones 57 in 28% yield [88JCS(D)433]. 

Pyrido[ 1,2-a]pyrimidine-6-thione 231 was prepared in the reaction of pyridinethione 229 and benzylidenemalononitrile in boiling dioxane in the presence of a catalytic amount of piperidine [93JCR(S)8]. 6H-Pyrido[l, 2-a]pyrimidine-6-thione 231 was also obtained when pyridinethione 229 was reacted with benzaldehyde in the presence of a few drops of piperidine for 2 hours, and then condensation product 230 was reacted with malononitrile. 

Ethyl-2-methyl-4//-pyrido[l,2-a]pyrimidin-4-thione was obtained in... 

Reaction of 4-cyano-l -oxo-2,3-dihydro-l H-pyrido [1,2-c] pyrimidine-3-thione 72 with halogeno ketones 73 afforded tricyclic derivatives 74 (08MI2). 

Alkylation of l-aryl-4-cyano-l-trifluoromethyl-2,3-dihydro-lH-pyrido [l,2-c]pyrimidine-3-thiones with benzyl bromides, ethyl 2-broroacetate, and 2-chloroacetamides in the presence of K2C03 in DMF at ambient temperature gave 3-[(substituted methyl)thio)]-lH-pyrido[l,2-c]pyrimi-dines in 51-87% yields (07MI1). 

Cyclocondenzation of 2-pyridylacetonitrile and ethoxycarbonyl isothiocyanate in MeCN gave 4-cyano-l-oxo-2,3-dihydro-lH-pyrido[l,2-c]pyrimi-dine-3-thione in 18% yield (08MI2). 6-Endo-trig cyclization of anion, formed from 4-methylpyrimidine by LDA in THF at —78 °C, with methyl 3-propynoate provided 8-methyl-6H-pyrido[2,l-c]pyrimidin-6-one in 47% yield (06TL5063). 

P2S3)2 (93MIP4), and that of l,3,3-trimethyl-9-phenyl-l,2,3,6,7,8-hcxahydro-4//-pyrido[l, 2-a]pyrimidine-2,4-dione with Lawesson s reagent (96H(42)117) afforded 4-thione and 2,4-dithione derivatives, respectively. 

Acetyl-4-phenylamino-2if-pyrido[l, 2-a]pyrimidin-2-one (285) was obtained when A-(2-pyridyl)acetoacetamide 332 (R = H) was first treated with PhNCS in the presence of K2CO3 and BnEtsNCl, then with Mel and NEt3, and then the reaction mixture was heated rapidly to 80 °C (95MI2). Reaction of A-(2-pyridyl)acetoacetamides 332 with CS2 in the presence of K2CO3 and a catalytic amount of BnEt3NCl, then with 1 or 2 equiv of Mel afforded 3-acetyl-2-hydroxy-4Ef-pyrido[l,2-<2]pyrimidine-4-thiones 333 and 3-acetyl-4-methylthio-2i/-pyrido[l,2-a]pyrimidin-2-one (334), respectively (96MI22). 

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