Pyrimido diones

Carboxy substituted diazepines 226 and 229 react with phenyl isocyanate to afford pyrimido diones 227 and 230, correspondingly (Scheme 48, Section 3.1.1.3 (1993JHC897)). N-Hydroxymethylation on an indole ring annulated to benzaze-pinone, as well as formation of the corresponding carbamate and urea, has been described (2004MI1076). 

Pyrimido[4,5- f]pyrimidines may be used as pyrimidine precursors. Thus, the dihydro derivative (736) undergoes alkaline hydrolysis to the amide (737 R = PrCO) which may be deacylated in ethanolic hydrogen chloride to give 5-aminomethyl-2-propylpyrimidin-4-amine (737 R = H) (64CPB393) rather similarly, the pyrimidopyrimidinedione (738) reacts with amines to give, for example, 6-amino-5-benzyliminomethyl-l,3-dimethylpyrimidine-2,4(lFf,3Ff)-dione (739 R = CH2Ph) or the hydrazone (739 R = NH2) (74JCS(Pl)1812). 

Finally, 4-aminopyrimidine-5-carbaldehydes with cyclic jS-diketones, such as cyclo-hexane-l,3-dione, give partially reduced pyrimido[4,5-f>]quinolones (239) (76JOC1058). 

Pyrimido[4,5-c]pyridazine-5,7-dione, 3-aryl-6,8-dimethyl-synthesis, 3, 357... 

Pyrimido[4,5-d]pyridazine-5,8-dione, 2-aryl-chlorination, 3, 345 Pyrimido[ 1,2-6]pyridazine-2,4-diones synthesis, 3, 355... 

Pyrimido[5,4-c]pyridazine-6,8-diones synthesis, 3, 357 Pyrimidopyridazines rearrangement, 5, 342 Pyrimido[ 1,2- 6]py ridazines HNMR, 3, 334 reactivity, 3, 343... 

Pyrimido[4,5-d]pyrimidine-2,4-dione, 5-amino-7-methylthio-synthesis, 3, 364... 

Pyrimido[4,5-d]pyrimidine-5,7-diones synthesis, 3, 363 Pyrimidopyrimi dines synthesis, 4, 507 Pyrimido[ 1,2-a]pyrimidines reaetivity, 3, 348 strueture, 3, 337-338 synthesis, 3, 360 Pyrimido[ 1,6-a]pyrimidines reaetivity, 3, 349 structure, 3, 338 synthesis, 3, 362 Pyrimido[l, 6-c]pyrimidines reaetivity, 3, 349 strueture, 3, 338 synthesis, 3, 362 Py rimi do[4,5-djpyri midi nes applieations, 3, 368 eleavage, 3, 350 reaetions... 

PyrimidoX4,5-6]quinoline-2-carboxylic acids synthesis, 3, 224-225 Pyrimido[4,5-6]quinoline-2,4-diones synthesis, 3, 224 Pyrimido[5,4-6]quinolinediones synthesis, 3, 219 Pyrimido[4,5-6]quinolines synthesis, 3, 219, 224, 227, 228, 230, 231 Pyrimido[4,5-c]quinolines synthesis, 3, 224, 227 tautomerism, 3, 205 Pyrimido[5,4-6]quinolines synthesis, 3, 227 Pyrimido[5,4-c]quinolines synthesis, 3, 219, 224, 227, 230 Pyrimido[5,4-6]quinoline-1,3,5-trione, 7-chloro-synthesis, 3, 221... 

Pyrimido[5,4-e][l,2,4]triazine-5,7-dione, N-methyl-applications, 3, 456 Pyrimido-1,2,4-triazinediones synthesis, 2, 78 Pyrimidotriazines synthesis, S, 338... 

Cyclization of the 5-(A -arylcarboxamido)-4-hydrazino-6methylpyrim-idin-2-ones 104 with two molar equivalents of formaldehyde in the presence of pyridine caused the concomittant triazole and pyrimidine ring formation to yield the 4-aryl-l,3,4,10-tetrahydro-6-methyl-l,2,4-tria-zolo-[2,3,4-c,d]pyrimido[4,5-d]pyrimidine-5,8-diones 105 (89AP599)... 

Characteristic H NMR data of (4a/ ,55)- and (4n5,5R)-2-substituted 5- [A-(/e/ /-butoxycarbonyl)-L-tryptophyl]amino perhydropyrido[l,2-c]pyri-midine-l,3-diones were tabulated (01JMC2219). C CPMASS NMR data of 4-(4-methoxyphenyl)perhydropyrido[l,2-c]pyrimidine were reported (00JST73). C NMR data were reported for eight 4-aryl-2,3,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidin-l,3-diones in the solid state and in CDCI3 solution (00JPO213). The structure of 4-aryl-3,4-dihydro-2//-pyrido [l,2-c]pyrimidine-l,3-diones and their 2,3,5,6,7,8-hexahydro derivatives were characterized by H and C NMR data (99JHC389). Conformational analysis of 6-methyl-2,3,4,6,7,ll/)-hexahydro-l//-pyrimido[6,l-n]isoquino-lin-2-ones 138 and 139 were carried out by H and C NMR studies (97LA1165). 

The mass spectral fragmentations of 9,10-dimethoxy-2,3,4,6,7,ll/)-hexa-hydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140 and -2,4-diones 141, under electron ionization (at 70 eV) were examined by metastable ion analysis, a collosion-induced dissociation technique and exact mass measurement (97RCM1879). Methyl substituent on N(3) in 140 (R = Me) had a larger effect on both the fragmentation and on the peak intensities, than a methyl substituent on C(6) (R = Me). The ionized molecules of 140 (R = H) were rather stable, whereas 4-phenyl substitution on C(4) of 140 (R = Ph) promoted the fragmentations of the molecular ions. The hexahydro-1//-pyrimido[6,l-n]isoquinoline-2,4-diones 141 were more stable, than the hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones 140, and the molecular ions formed base peaks. 

Cyclocondensation of a-aryl-2-pyridylacetamides and 2-(3,4-dihydroiso-quinolin-l-yl)acetamide with Et2C03 in the presence of NaOEt in boiling EtOH afforded 4-aryl-2,3-dihydro-l//-pyrido[l,2-c]pyrimidine-l,3-diones (99JHC389) and 6,7-dihydro-4//-pyrimido[6,1 -a]isoquinoline-2,4-dione (98MIP15), respectively. 

Pyrimido[5, 4 4,5]pyrazolo[3,2-c][l,2,4]triazine derivatives 1049and 1050 were prepared by treatment of diazo compound 1048, prepared from 1047, with pentane-2,4-dione and ethyl acetoacetate, respectively [92JCS(Pl)239]. 

The bromine atom of 4-aryl-2-(4-bromobutyl)-2,3,5,6,7,8-hexahydro-177- ancj -perhydropyrido[l,2-c]pyrimidine-l,3-diones was displaced with 4-substituted piperazines <2002FES959, 2004APH139, 2004PHA99>. Heating 3-hydroxymethyl derivatives of epimeric 6-methyl-l,3,4,6,7,llb-hexahydro-277-pyrimido[6,l-,2]isoquinolin-2-ones 152 resulted in the formation of the 3-unsubstituted derivatives 153 by loss of CH20 (Equation 26) <1997LA1165>. 

Heating 2-(arylaminothiocarbonyl)-T(2-hydroxyethyl)-l,2,3,4-tetrahydroisoquinolines in EtOH in the presence of HC1 afforded 4-arylimino-l,6,7,llb-tetrahydro-2/7,477-[l,3]thiazino[4,3-tf]isoquinolines <2001ARK33>. 1,3,4,6,7,11b-Hexahydro-2/7-pyrimido[6,l-+]isoquinoline-2,4-diones were obtained by the cyclization of 2-(2-aminocarbonyl-l,2,3,4-tetrahydroisoquinolin-l-yl)acetates on the action of a base <2004MOL694>. 

Treatment of pyrimidine-2-thione 184 with A1C13 yielded 6-oxo-6,7-dihydro-4//-pyrimido[6,l-tf]isoquinolin-4-thione 185 (Equation 37) <1998MI337>. Cyclization of 6,7-diethoxy-2-propylaminocarbonyl-l,2,3,4-tetrahydroisoquinoline-l-acetonitrile using NaOMe afforded 9,10-diethoxy-2-imino-3-propyl-l,2,4,6,7,l lb-hexahydropyrimido[6,l-tf]isoquinolin-4-one <1995S863>. Cyclization of l-(2-carboxyethyl)-l,2,3,4-tetrahydroquinazoline-2,4-dione 186 in polyphosphoric acid (PPA) afforded l,2,3,5,6,7-hexahydropyrimido[3,2,T /]quinazoline-l,3,7-trione 187 (Equation 38) <1997CHE96>. 

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