Isoquinoline-l-thiones

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). 

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>. 

Attaching cyclic, bidentate 1-hydroxy-177-pyridin-2-thione, 1-hydroxy-177-pyridin-2-one (1,2-HOPO) and 2-hydroxy-277-isoquinolin-l-one (1,2-HOIQO) ligating units via their C-6 carbon to TREN template produced 19 , 20 and 21 , respectively. 

For the bicyclic compounds the differences in aromaticity between the two possible forms were smaller, about 8 and about 18 kJ mol-1 for the quinolin-2-one and isoquinolin-l-one systems respectively. Similar values were found for the corresponding bicyclic thiones. 

Cycloaddition of 2-ethoxy-2,3-dihydro-4//-1,3-benzoxazin-4-one with conjugated diene 167 gave tetrahydropyrido[2,l-b][l,3]oxazin-6-ones (168) (71JHC865). Diels-Alder reactions of 3,4-dihydroisoquinolines and thioketenes (169), formed in situ, yielded 4,6,7,116-tetrahydro[l,3]ox-azino[2,3-a]isoquinoline-4-thiones [83AG(E)55 88CB1165],... 

Phenylimino)-l-hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,ll -hexahy-dro[l,3]oxazino[4,3-a]isoquinoline was prepared from 4-methylimino and 4-thione derivatives in the presence of HgO and 4-methylthio-l,6,7,llh-tetrahydro-2//-[l,3]oxazino[4,3- ]isoquinolinium salt with aniline (85GEP3510526). 4-Methylthio-l-hydroxymethyl-9,10-dimethoxy-l,6,7,116-tetrahydro-2//-[l,3]oxazino[4,3-a]isoquinolinium iodide was obtained from the l,2,4,6,7,116-hexahydro-4-thione derivative with methyl iodide (85GEP3510526). 1-Hydroxymethyl-9,10-dime thoxy-1,2,4,6,7,116-hexahy-dro-[l,3]oxazino[4,3-fl]isoquinolin-4-thione was obtained from its 4-one derivative by treatment with P4S10 in pyridine (85GEP3510526). 

The reaction of l,3,4,4a,5,10-hexahydro[l,3]thiazino[3,4-ft]isoquinoline-1-thione and methyl iodide gave l-methylthio-4,4a,5,10-tetrahydro-3//-[l,3]thiazino[3,4-6]isoquinolinium iodide, which reacted with 5-aminoiso-quinoline in pyridine at 40°C to afford l-(5-isoquinolylimino)-l,3,4,4a,5, 10-hexahydro[l,3]thiazino[3,4-b]isoquinoline (79GEP2848926). 

Structures of 3-[(4-methylphenyl)amino]-47/-pyrido[l,2-tf]pyrazine-4-thione, iV-tosyl-3-[(4-methylphenyl)a-mino]-4//-pyrido[l,2-tf]pyrazine 4-imine, and 246 were confirmed by X-ray investigations <1999JPR332>. The stereostructures of (4A,llaA)-lla-ethoxycarbonylT,3,4,6,lla-hexahydro-l,3,4,6,ll,lla-hexahydro-4-methox-ycarbonyl-l-oxo-[l,4]oxazino[4,3-A isoquinoline <1995ZK787>, 2//-pyrazino[l,2- ]isoquinolinc-l,4-dione 247 <2001TL543>, 4-benzyl-2-methyl-1,3,4,6,7,11 b-hcxahydro-2//-pyrazino[2,l -zz] isoqu incline-3,6-dione... 

Perhydropyrido[l,2-c][l,3]oxazin-l-ones were prepared in the reaction of the appropriate 2-(2-piperidyl)ethanols and ethyl chloroformate (63AP38) in the presence of sodium ethylate in boiling benzene, or when 2-(2-piperidyl)ethanol was reacted with dimethyl carbonate in the presence of sodium methylate (91X1311). l-Hydroxymethyl-9,10-dimethoxy-l,2,4,6,7,llb-hexahydro-[l,3]oxazino[4,3-fl]isoquinoline-4-oneand 4-thione were prepared from l-[bis(hydroxymethyl)methyl]-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline with ethyl chloroformate in the presence of sodium methylate, and thiophosgene in the presence of NEts, respectively... 

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