4- Substituted-2-methyl-6//-pyrimido

A six-step approach to 6-phenylthio-substituted 2,3,4,5-tetrahydro-l,3-l//-diazepin-2-ones based on a ring-expansion reaction of 4-mesyloxymethyl-l,2,3,4-tetrahydropyrimidin-2-ones under the action of nucleophiles has been achieved. The thermal rearrangement of (6-oxo-l,6-dihydropyrimidin-2-yl)guanidines with triethyl orthoacetate to give 4-substituted-2-methyl-6//-pyrimido[l,2-a][l,3,5]triazm-6-ones has been reported (Scheme 16) ... 

Cyclocondenzation of 2-aminoquinoline and isopropylidene 2-(l-methylthioalkylidene)malonates on Si02 under microwave irradiations afforded 3-substituted (3-methylthio, 3-methyl, 3-ethyl, and 3-phenyl) l//-pyrimido[l, 2-n]quinolin-1-ones (00MI40). 

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. 

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>. 

Only two examples of the synthesis pyrimidoazocines have been described. In Ref. 82JHC1257, a three-stage synthesis of a new heterocycle system, pyrimido[5,4-c]benz[l]azocine, has been proposed. Condensation of 4-methyl-2-phenyl-5-pyrimidincarboxylate (112) with 3,4-dimethoxy-6-nitrobenzaldehyde (113) led to the substituted alkene 114, which, after catalytic hydrogenation of the nitro group on Raney nickel and subsequent intramolecular cyclization of product 115, was converted into pyrimidobenz[l]azocine 116 (Scheme 32). 

Murata T, Balodis K, Saito G (2008) Single-component organic conductors based on neutral betainic radicals of A-methyl substituted dioxo- and aminooxo-pyrimido-fused TTFs. Synth... 

C-Alkylation of 1-methyl-1,2,3,4-tetrahydro-6//-pyrimido[l,2-b]isoquino-lin-6-one with benzyl bromide in boiling methylene chloride overnight in the presence of potassium carbonate, and with excess methyl iodide gave 11-substituted derivatives (113 and 114) (88HCA77). The treatment of hydrobromide salt of 11-benzyl derivative 113 with a base yielded 11-benzyl-1 -methyl-1,2,3,4-tetrahydro-6//-pyrimido[l, 2-6]isoquinolin-6-one (115). 

Pyrimido[4,5-6][l,4]thiazines (262) have been prepared by cyclocondensation of the aminothiols (260) with methyl trifluoropyruvate (261) in benzene (89KGS1492), or with 4-substituted 3-halo-2,4-dioxobutyric acid esters (263) at pH 2-5 in DMF to give 6-carbethoxy-7-acyl derivatives of 5H-pyrimido[4,5-6][l,4]thiazines (264) (Equations (38) and (39)). 

The 4-oxo group of l-methyl-5-(2-bromoethyl)uracil is substituted by 1,2,4-triazoles using the system POCl3/NEt3/MeCN. Hydroxylamine hydrochlorides lead, in turn, to 3,4-dihydro-6//,8//-pyrimido[4,5-c][l,2]oxa-zine-7-ones (89H1735) (Scheme 127). 

NMR data on 2-oxo-, 3-methyl-, and 3-phenyl-2,4-dioxo-l,3,4,6,7,l Ih-hexahydropyrimido[6,l-a]isoquinolines have been measured in CDCI3 (91MRC10 ). The structures of 3-amino-4-substituted 1,3,4,6,7,llh-hexa-hydro-2//-pyrimido[6,l-a]isoquinoline-2-ones have similarly been investigated by means of NMR spectroscopy (90JHC957). 

Reduction of 9,10-dimethoxy-l-(un)substituted 3-substituted 1,3,4,6,7, llh-hexahydro-2//-pyrimido[6,l-a]isoquinolones with NaBH4 in acetic acid afforded ring-opened 6,7-dimethoxy-2-methyl-l-[2-(substituted amino)-2-oxo]ethyl-l,2,3,4-tetrahydroisoquinolines (92GEP4104257). 

Still other SAR studies included pyrimido[4,5-d]pyrimidine-2,4(l//,3//)dione and 2,4(l//,3//)-pteridinedione nucleosides as antiviral agents, 2-ary 1-6,8-disubstituted-quinazol-4(3//)-ones as fungicides <97IJHC51>, 3-N-substituted-thioureido-2-methyl-6-phenylthieno-[3,2-d]pyrimidin-4(3//)-ones <97JIC160> and 2-(dialkylamino, piperidino, morpholinomethyl)-... 

Several substituted 2-ethynylbenzaldehydes were then apphed to this copper-catalyzed four-component synthesis of 3,4-dihydro-2ff-pyrimido[2,l-fl]isoquino-Une under optimized conditions (Table 1, entry 10). The results are summarized in Table 2. The substitution by a fluorine atom at the para-position to the formyl group shghtly decreased the yield of 12b (55%, entry 1). The reaction with 2-ethynylbenzaldehydes Ic and Id containing a fluorine atom at the meta-position or methyl group at the para-position to the formyl group showed a good conversion to yield the desired tricyclic compounds 12c and 12d (74 and 71%, respectively, entries 2, 3). The use of 2-ethynyl-5-methoxybenzaldehyde le also gave tricyclic compound 12e (55%, entry 4). Overall, this four-component construction of 3,... 

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