HETEROCYCLES

Paper | Special issue | Vol. 80, No. 1, 2010, pp. 379-393
Received, 9th June, 2009, Accepted, 31st July, 2009, Published online, 5th August, 2009.
DOI: 10.3987/COM-09-S(S)33

■ Chemo- and Regioselective Imino Diels-Alder Reactions: Synthesis of Functionalized Novel Quinolin-3-one and Quinoline Derivatives

Chander Mohan, Gaurav Bhargava, and Mohinder P. Mahajan*

Department of Applied Chemistry, Guru Nanak Dev University, Amritsar 143 005, Punjab, India

Abstract

Regio- and catalyst selective imino Diels-Alder reactions of vinyl/isopropenyl pyrimidinones with N-arylimines in the presence of metal salts viz. magnesium(II) bromide, zinc(II) chloride, indium(III) chloride, yttrium triflate and scandium triflate, are described. An unprecedented oxidation of methylene to carbonyl has been shown to accompany the imino Diels–Alder reactions of isopropenyl pyrimidinones in the presence of yttrium and scandium triflates. Chemoselective effect of different Lewis acids used as catalysts in these reactions has been rationalized.

INTRODUCTION
The imino-Diels-Alder (IDA) reaction involving the coupling of imines, derived from aromatic amines, or their surrogates,1 with electron rich alkenes has emerged as a powerful tool for the synthesis of tetrahydroquinolines2 and allied substrates. Some of these substrates are known for their biologically latency viz. psychotropic, antiallergic, anti-inflammatory and estrogenic activities.3 There are numerous reports on the IDA reactions of N-arylimines with sterically unhindered activated alkenes, cyclopentadiene or symmetrical activated butadienes catalyzed by a variety of metal salts and protic acids.4, 5 Such reactions suffered from lack of chemoselectivity and resulted in formation of a mixture of adducts.4 However, the reports concerning the use of acyclic un-activated and sterically hindered alkenes as dienophiles in such IDA reaction are rare.5
In recent communications, we have compared the dienic properties of N-arylimines in their Lewis acid mediated cycloaddition reactions with 5-isopropenyl pyrimidinones and 3-dienyl-2-azetidinones (Figure 1). These reactions were shown to result in the formation of 5-quinoline substituted pyrimidinone/azetidinone derivatives with participation of N-aryl imines as 4π component of 2-azadiene.6a, 6c In continuation of these studies, we report herein a detailed account of chemo- as well as regioselective metal salts or Lewis acid catalysed IDA reactions of 5-isopropenyl/vinyl pyrimidinones with N-arylimines. Interestingly, these reactions resulted in a catalyst selective formation of novel pyrimidinone tethered quinoline, dihydroquinoline and quinolin-3-one derivatives depending upon the nature of the metal salts or Lewis acid employed. Such functionalized pyrimidinones have been reported to show antitumour, antiviral, antitubercular, antifungal, molluscidal and larvacidal activities.7

RESULTS AND DISCUSSION
Different Lewis acids viz. magnesium(II) bromide, zinc(II) chloride, indium(III) chloride, yttrium triflate and scandium triflate were selected for examination of their effects on the chemo- and regioselectivities of the IDA reactions of 1 with N-arylimines 2.
The reactions of 1a-b with N-arylimines 2a-c in the presence of yttrium triflate as Lewis acid catalyst resulted in the formation of 5-quinoline substituted pyrimidinone derivatives 4a-f in good yields (Table 1, Entries 1-3). The reactions in the presence of scandium triflate, magnesium(II) bromide, zinc (II) chloride and indium(III) chloride (Table 1, Entries 4-15), were found to be slower and required longer reaction periods for their completion with the formation of 4a-f in moderate to good.
The products were characterized on the basis of analytical and spectral data, as described in the experimental section while the salient features are mentioned here. The compound 4a, for example, showed a [M+1]+ peak at m/z 516 in its mass spectrum. Its IR spectrum showed a strong absorption at 1670 cm-1 due to the carbonyl group of the pyrimidinone ring. Its 1H NMR (300 MHz) spectrum showed singlets at δ 7.97 and δ 8.55 assigned to H6 of the pyrimidinone ring and H8 of the quinoline ring, respectively. The formation of pyrimidinones 4 in these reactions presumably involves regioselective IDA reactions of vinyl pyrimidinones 1 with N-arylimines 2 participating as 2-azadienes leading to the initial formation and subsequent aromatization of cycloadducts 3.8

In order to extend the scope of such studies to the IDA reactions of sterically more hindered alkenes, we have examined the reactions of 5-isopropenyl pyrimidinones 5 with N-arylimines 2 in the presence of various (lanthanide and non-lanthanide) Lewis acid catalysts. Interestingly, these reactions in the presence of 10 mol % of Y(OTf)3 and Sc(OTf)3 in acetonitrile resulted in regio- and chemoselective formation of 6-oxo-1,6-dihydropyrimidin-5-yl-4H-quinolin-3-one derivatives 6 (Scheme2; Table 2; Entries 1-8). The yields of the oxidized cycloadducts were found to be higher in presence of Y(OTf)3 (Entries 1-4) as compared to Sc(OTf)3 (Table 2, entry 5-7).

The structure 6 was assigned to the products with the help of analytical data and spectral evidences. The pyrimidinone 6a, for example, exhibited a molecular ion peak at m/z 546 in its mass spectrum. Its IR spectrum showed the pyrimidinone and pyridone carbonyl absorptions at 1666 cm-1and 1687 cm-1 respectively. Its 1H NMR spectrum showed the absence of methylene protons, the presence of a three proton singlet at δ 1.73 due to the methyl protons of the quinoline-3-one ring and a characteristic singlet at δ 8.34 for the olefinic proton of the pyrimidinone ring. Its 13C NMR spectrum showed pyrimidinone and quinolinone carbonyls at δ 160.5 and 193.7 ppm, respectively. The assigned structure 6a was unambiguously established with the help of X-ray crystallographic studies.6a
The precise mechanism for the oxidation of methylene to carbonyl observed in these reactions could not be ascertained, however, it may involve a mechanism similar to the one observed in Yb(OTf)3.9 Alternatively, it may take place via a charge transfer complex followed by the formation of radical cation as observed in Ce(OTf)3.10
However, the reactions of pyrimidinones 5a-b with 2a-c in the presence of non-triflate Lewis acid catalysts, viz MgBr2, InCl3, ZnCl2 and resulted in the formation of previously unreported 3, 4-dihydroquinolin-4-ylpyrimidin-4-one derivatives 7a-f in good yields (Table 2; Entries 9-20). The use of magnesium (II) bromide as catalyst resulted in better yields of adducts while moderate yield of adducts 7 were obtained when indium (III) chloride and zinc (II) chloride were used as catalysts.

Thus, the oxidation of methylene to carbonyl, observed in reactions of 5a-c with 2a-d in the presence of Y(OTf)3/ Sc(OTf)3 as catalysts, was not observed when these reactions were performed in the presence of non-triflate LA catalysts. The structure 7 was also assigned on the basis of analytical data and spectral evidences. The 1H NMR spectrum of 7a exhibited characteristic doublets at δ 2.35 (J=16.5Hz) and δ 4.35 (J=16.5Hz) assigned to the methylene protons of the quinoline ring. The methylene carbon of the quinoline ring appeared at δ 38.4 in its 13C NMR. The oxidation of methylene to carbonyl in the presence of Y(OTf)3/ Sc(OTf)3 catalysts is also supported by the independent transformation of 7 to 6 in the presence of 10 mol% of Y(OTf)3 / Sc(OTf)3 in acetonitrile at room temperature.

CONCLUSION
In conclusion, this manuscript describes the regio- and catalyst selective Imino Diels–Alder reactions of sterically hindered and geminally di-substituted alkenes viz. 5-vinyl and isopropenyl-pyrimidinones with N-arylimines. The reactions resulted in the synthesis of quinoline-tethered pyrimidinone derivatives in case of vinyl-pyrimidinones 1a-b using triflate as well as non-triflate Lewis acid catalysts, since aromatization of initial IDA adducts is a favored process. However, in case of isopropenyl-pyrimidinones 5a-c, where aromatization of IDA adducts is not possible due to the presence of the methyl group, the reactions accompanied an unprecedented oxidation of methylene to carbonyl in the presence of Y(OTf)3/ Sc(OTf)3 leading to the formation of quinolone substituted pyrimidinone derivatives.

EXPERIMENTAL
General Remarks
Melting points were determined by open capillary using a Veego Precision Digital Melting Point apparatus (MP-D) and are uncorrected. IR spectra were recorded on a Shimadzu D-8001 spectrophotometer. 1H NMR spectra were recorded in deuteriochloroform with a Joel (300 MHz) spectrometers using TMS as internal standard. Chemical shift values are expressed as ppm downfield from TMS and J values are in Hz. Splitting patterns are indicated as s: singlet, d: doublet, t: triplet, m: multiplet, q: quartet, br: broad peak and brs: broad singlet. 13C NMR spectra were also recorded on a Joel 300 (75.0 MHz) spectrometers in deuteriochloroform using TMS as internal standard. Mass spectra were recorded on a Shimadzu GCMS-QP-2000 mass spectrometer. Elemental analyses were performed on a Heraus CHN-O-Rapid Elemental Analyzer. Column chromatography was performed on a silica gel (60–120 mesh).

GENERAL PROCEDURE
5-Vinyl/isopropenyl pyrimidinones were prepared by the reported methods.11 The typical procedure for IDA reactions involved the addition of 10 mol % of Lewis acid to a well stirred solution of N-arylimine (1 mmol ) in dry acetonitrile (10 mL) at rt. The solution was allowed to stir for 5-min. followed by the addition of vinyl/isopropenyl pyrimidinones (1 mmol). The progress of the reaction was monitored by tlc using pyrimidinone as the limiting reactant. On completion, the reaction mixture was quenched with a water/MeOH mixture, extracted with CH2Cl2 and concentrated under reduced pressure. Column chromatography of the crude reaction mixture using a mixture of EtOAc: hexane (1:4) as an eluent resulted in the products which were recrystallized using a mixture of hexane: DCM (5:1).

5-[2-(4-Chlorophenyl)-6-methoxy-quinolin-4-yl]-2,3-diphenyl-3H-pyrimidin-4-one 4a.
Yellow solid; mp 165-166 0C ; IR (KBr) νmax 1670 cm-1; 1H NMR (300 MHz, CDCl3) : δ 3.88 (s, 3H, OCH3), 7.06- 7.50(m, 14H, ArH), 7.97(s, 1H, H8), 8.12 (m, 3H, H11, H12, H14), 8.55(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 55.7 (-OCH3), 101.8, 114.2, 122.0, 124.4, 126.3, 127.2, 127.9, 128.4, 128.8, 129.0, 129.2, 129.7, 131.4, 134.5, 134.8, 137.5, 138.6, 144.4, 150.2, 153.5, 155.4, 155.6, 158.2, 161.2.; MS m/z [M+1]+: 516; Anal. Calcd for C32H22ClN3O2 : C, 74.49; H, 4.30; N, 8.14. Found: C, 74.54; H, 4.82; N, 8.02.

5-(6-Methoxy-2-phenylquinolin-4-yl)-2,3-diphenyl-3H-pyrimidin-4-one 4b.
Yellow solid; mp 171-172 0C; IR (KBr) νmax 1667 cm-1; 1H NMR (300 MHz, CDCl3) : δ 3.81 (s, 3H, OCH3), 7.04- 7.55(m, 15H, ArH), 7.98(s, 1H, H8), 8.10 (m, 3H, H11, H12, H14), 8.52(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 56.2 (-OCH3), 101.1, 113.9, 121.8, 123.8, 126.5, 127.1, 127.5, 128.3, 128.7, 129.2, 129.4, 129.8, 131.2, 134.4, 134.7, 137.6, 138.3, 144.5, 149.9, 153.6, 155.6, 155.7, 158.3, 161.2.; MS m/z [M+1]+ : 482; Anal. Calcd for C32H23N3O2 : C, 79.81; H, 4.81; N, 8.73. Found: C, 79.74; H, 4.72; N, 8.65.

5-[6-Methoxy-2-(4-methoxyphenyl)-quinolin-4-yl]-2, 3-diphenyl-3H-pyrimidin-4-one 4c.
Yellow solid; mp 159-160 0C; IR (KBr) νmax 1672 cm-1; 1H NMR (300 MHz, CDCl3) : δ 3.79 (s, 3H, OCH3), 3.88 (s, 3H, OCH3), 7.10- 7.46(m, 14H, ArH), 7.98(s, 1H, H8), 8.10 (m, 3H, H11, H12, H14), 8.52(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 56.0(-OCH3), 56.2 (-OCH3), 100.9, 114.0, 121.6, 123.5, 126.7, 126.8, 127.6, 128.4, 128.6, 129.3, 129.5, 129.9, 130.9, 133.8, 134.2, 137.2, 138.0, 144.1, 149.7, 153.5, 155.4, 155.8, 158.2, 161.3.; MS m/z [M+1]+ : 512; Anal. Calcd for C33H25N3O3 : C, 77.48; H, 4.93; N, 8.21. Found: C, 77.35; H, 4.82; N, 8.05.

5-(6-Methoxy-2-phenylquinolin-4-yl)-2-phenyl-3-p-tolyl-3H-pyrimidin-4-one 4d.
Yellow solid; mp 162-163 0C; IR (KBr) νmax 1665 cm-1; 1H NMR (300 MHz, CDCl3) : δ 2.28 (s, 3H, CH3), 3.74(s, 3H, OCH3), 7.12-7.48(m, 14H, ArH), 8.05 (s, 1H, H8), 8.09 (m, 3H, H11, H12, H14), 8.35(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 16.7(CH3), 56.2(-OCH3), 101.2, 114.1, 121.9, 123.8, 125.8, 126.3, 127.3, 128.0, 128.7, 129.2, 129.6, 130.3, 131.3, 134.1, 134.6, 137.5, 138.8, 144.2, 150.5, 153.5, 155.6, 155.7, 158.5, 161.0.; MS m/z [M+1]+ : 496; Anal. Calcd for C33H25N3O2 : C, 79.98; H, 5.08; N, 8.48. Found: C, 79.73; H, 5.13; N, 8.52.
5-[2-(4-Chlorophenyl)-6-methoxy-quinolin-4-yl]-2-phenyl-3-p-tolyl-3H-pyrimidin-4-one 4e.
Yellow solid; mp 176-177 0C; IR (KBr) νmax 1668 cm-1; 1H NMR (300 MHz, CDCl3) : δ 2.31 (s, 3H, CH3), 3.86 (s, 3H, OCH3), 7.02- 7.52(m, 13H, ArH), 7.94(s, 1H, H8), 8.13 (m, 3H, H11, H12, H14), 8.55(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : δ 19.6 (-CH3), 55.9 (-OCH3), 101.6, 114.4, 122.2, 124.5, 126.6, 127.4, 127.9, 128.5, 128.7, 129.0, 129.4, 129.8, 131.5, 134.6, 134.9, 137.5, 138.6, 143.9, 153.5, 155.5, 155.7, 158.2, 161.0.; MS m/z [M+1]+ : 530; Anal. Calcd for C33H24ClN3O2 : C, 74.78 ; H, 4.56; N, 7.93. Found: C, 74.80; H, 4.62; N, 7.85.

5-[6-Methoxy-2-(4-methoxyphenyl)-quinolin-4-yl]-2-phenyl-3-p-tolyl-3H-pyrimidin-4-one 4f.
Yellow solid; mp 178-179 0C; IR (KBr) νmax 1666 cm-1; 1H NMR (300 MHz, CDCl3) : δ 2.32 (s, 3H, CH3), 3.88 (s, 6H, OCH3), 7.09- 7.59(m, 13H, ArH), 7.98(s, 1H, H8), 8.15 (m, 3H, H11, H12, H14), 8.50(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : δ 19.9 (-CH3), 55.8 (-OCH3), 56.0 (-OCH3), 100.6, 113.9, 122.5, 123.9, 126.4, 127.7, 128.1, 128.7, 128.9, 129.2, 129.4, 129.9, 131.4, 134.3, 134.8, 137.3, 138.3, 143.7, 153.6, 155.3, 155.9, 158.4, 160.8; MS m/z [M+1]+ : 526; Anal. Calcd for C34H27N3O3 : C, 77.48 ; H, 5.18; N, 7.99. Found: C, 77.80; H, 5.22; N, 7.86.

2-(4-Chlorophenyl)-6-methoxy-4-methyl-4-(6-oxo-1,2-diphenyl-1,6-dihydropyrimidin-5-yl)-4H-quinolin-3-one 6a.
Yellow solid; mp 146-147 0C; IR (KBr) νmax 1666, 1687 cm-1; 1H NMR (600 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 3.84 (s, 3H, OCH3), 6.65-7.99 (m, 17H, ArH), 8.34(s,1H olefinic proton), 13C NMR (150 MHz, CDCl3) : 24.8(-CH3), 51.1(C-7, quinolin-3-one ring), 55.5(-OCH3), 111.4, 112.7, 123.6, 127.9, 128.0, 128.4, 128.6, 128.65, 128.8, 129.0, 129.2, 129.8, 129.9, 132.7, 134.3, 134.9, 135.3, 136.6, 138.8, 149.4, 154.1, 159.3, 160.3, 160.5 (C=O, pyrimidinone ring), 193.7 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 546; Anal. Calcd for C33H24ClN3O3 : C, 72.59; H, 4.43; N, 7.70. Found: C, 72.71; H, 4.54; N, 7.79.

6-Methoxy-4-methyl-4-(6-oxo-1,2-diphenyl-1,6-dihydropyrimidin-5-yl)-2-phenyl-4H-quinolin-3-one 6b.
Yellow solid; mp 149-150 0C; IR (KBr) νmax 1665, 1689 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 3.86 (s, 3H, OCH3), 6.69-7.98 (m, 18H, ArH), 8.35(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.5(-CH3), 51.2(C-7, quinolin-3-one ring), 55.6(-OCH3), 111.2, 112.6, 123.5, 127.9, 128.1, 128.3, 128.5, 128.6, 128.9, 129.0, 129.3, 129.7, 129.8, 132.6, 134.4, 134.8, 135.4, 136.6, 138.8, 149.5, 154.2, 159.1, 160.2, 160.5 (C=O, pyrimidinone ring), 193.5 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 512; Anal. Calcd for C33H25N3O3 : C, 77.48; H, 4.93; N, 8.21. Found: C, 77.66; H, 4.84; N, 8.34.

6-Methoxy-2-(4-methoxyphenyl)-4-methyl-4-(6-oxo-1,2-diphenyl-1,6-dihydropyrimidin-5-yl)-4H- quinolin-3-one 6c.
Yellow solid; mp 155-156 0C; IR (KBr) νmax 1665, 1688 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.72(s, 3H, CH3), 3.86(s, 3H, OCH3), 3.88 (s, 3H, OCH3), 6.66-7.94 (m, 17H, ArH), 8.34(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.4(-CH3), 51.0(C-7, quinolin-3-one ring), 55.5(-OCH3), 55.6(-OCH3), 111.3, 112.6, 123.6, 127.8, 128.1, 128.2, 128.4, 128.6, 128.8, 129.1, 129.4, 129.7, 129.9, 132.5, 134.4, 134.7, 135.6, 136.5, 138.9, 149.4, 154.0, 159.2, 160.3, 160.4 (C=O, pyrimidinone ring), 193.6 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 542; Anal. Calcd for C34H27N3O4 : C, 75.40; H, 5.02; N, 7.76. Found: C, 75.54; H, 5.55; N, 7.45.

6-Methoxy-4-methyl-4-(6-oxo-1,2-diphenyl-1,6-dihydropyrimidin-5-yl)-2-p-tolyl-4H-quinolin-3-one 6d.
Yellow solid; mp 132-133 0C; IR (KBr) νmax 1666, 1689 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 2.32 (s, 3H, CH3), 3.86(s, 3H, OCH3), 6.65-7.95 (m, 17H, ArH), 8.31(olefinic proton), 13C NMR (75 MHz, CDCl3) : 20.4(-CH3), 24.4(-CH3), 51.2(C-7, quinolin-3-one ring), 55.5(-OCH3), 111.1, 112.5, 123.4, 127.7, 128.0, 128.1, 128.4, 128.5, 128.7, 129.2, 129.5, 129.6, 129.8, 132.5, 134.5, 134.6, 135.7, 136.6, 138.8, 149.6, 154.1, 159.1, 160.2, 160.4 (C=O, pyrimidinone ring), 193.5 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 526; Anal. Calcd for C34H27N3O3 : C, 77.70; H, 5.18; N, 7.99. Found: C, 77.94; H, 5.35; N, 7.88.

2-(4-Chlorophenyl)-6-methoxy-4-methyl-4-(6-oxo-2-phenyl-1-p-tolyl-1,6-dihydropyrimidin-5-yl)-4H- quinolin-3-one 6e.
Yellow solid; mp 143-144 0C; IR (KBr) νmax 1665, 1687 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.72(s, 3H, CH3), 2.33 (s, 3H, CH3), 3.89(s, 3H, OCH3), 6.68-7.99 (m, 17H, ArH), 8.34(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.3(-CH3), 24.4(-CH3), 51.0(C-7, quinolin-3-one ring), 55.7(-OCH3), 111.1, 112.3, 123.5, 127.7, 128.0, 128.2, 128.3, 128.5, 128.6, 129.5, 129.6, 129.8, 129.9, 132.2, 134.3, 134.5, 135.7, 136.8, 138.6, 149.4, 154.3, 159.1, 160.2, 160.5 (C=O, pyrimidinone ring), 193.6 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 560; Anal. Calcd for C34H26ClN3O3 : C, 72.92; H, 4.68; N, 7.50. Found: C, 72.98; H, 4.55; N, 7.76.

6-Methoxy-4-methyl-4-(6-oxo-2-phenyl-1-p-tolyl-1,6-dihydropyrimidin-5-yl)-2-phenyl-4H-quinolin-3- one 6f.
Yellow solid; mp 140-141 0C; IR (KBr) νmax 1667, 1688 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.72(s, 3H, CH3), 2.31 (s, 3H, CH3), 3.86(s, 3H, OCH3), 6.66-7.97 (m, 17H, ArH), 8.33(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.5(-CH3), 24.3(-CH3), 51.1(C-7, quinolin-3-one ring), 55.6(-OCH3), 111.2, 112.5, 123.3, 127.6, 128.1, 128.3, 128.4, 128.6, 128.7, 129.4, 129.5, 129.7, 129.8, 132.6, 134.4, 134.5, 135.8, 136.7, 138.7, 149.5, 154.2, 159.0, 160.1, 160.5 (C=O, pyrimidinone ring), 193.7 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 526; Anal. Calcd for C34H27N3O3 : C, 77.70; H, 5.18; N, 7.99. Found: C, 77.88; H, 5.12; N, 7.92.

6-Methoxy-2-(4-methoxy-phenyl)-4-methyl-4-(6-oxo-2-phenyl-1-p-tolyl-1,6-dihydropyrimidin-5-yl)-4H-quinolin-3-one 6g.
Yellow solid; mp 138-139 0C ; IR (KBr) νmax 1666, 1689 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 2.31 (s, 3H, CH3), 3.86(s, 3H, OCH3), 3.87(s, 3H, OCH3), 6.67-7.95 (m, 17H, ArH), 8.32(olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.5(-CH3), 24.5(-CH3), 51.2(C-7, quinolin-3-one ring), 55.5(-OCH3), 55.6(-OCH3), 111.3, 112.5, 123.5, 127.8, 128.2, 128.3, 128.4, 128.5, 128.7, 129.4, 129.7, 129.8, 129.9, 132.1, 134.4, 134.6, 135.7, 136.7, 138.5, 149.5, 154.4, 159.2, 160.1, 160.4 (C=O, pyrimidinone ring), 193.5 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 556; Anal. Calcd for C35H29N3O4 : C, 75.66; H, 5.26; N, 7.56. Found: C, 75.77; H, 5.40; N, 7.42.

6-Methoxy-4-methyl-4-(6-oxo-2-phenyl-1-p-tolyl-1,6-dihydropyrimidin-5-yl)-2-p-tolyl-4H-quinolin-3- one 6h.
Yellow solid; m.p. 134-135 0C; IR (KBr) νmax 1665, 1688 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 2.31 (s, 3H, CH3), 2.33 (s, 3H, CH3), 3.87(s, 3H, OCH3), 6.66-7.98 (m, 17H, ArH), 8.34(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.5(-CH3), 19.8(CH3), 24.5(-CH3), 51.1(C-7, quinolin-3-one ring), 55.7(-OCH3), 111.1, 112.2, 123.4, 127.6, 128.3, 128.4, 128.6, 128.7, 128.9, 129.5, 129.7, 129.8, 129.9, 132.3, 134.5, 134.8, 135.7, 136.6, 138.8, 149.5, 154.5, 159.4, 160.1, 160.5 (C=O, pyrimidinone ring), 193.7 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 540; Anal. Calcd for C35H29N3O3 : C, 77.90; H, 5.42; N, 7.79. Found: C, 77.84; H, 5.40; N, 7.83.

2-(4-Chlorophenyl)-6-methoxy-4-[1-(4-methoxy-phenyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl]-4-methyl-4H-quinolin-3-one 6i.
Yellow solid; mp 136-137 0C; IR (KBr) νmax 1667, 1688 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.71(s, 3H, CH3), 3.86(s, 3H, OCH3), 3.88(s, 3H, OCH3), 6.64-7.95 (m, 17H, ArH), 8.32(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.8(-CH3), 51.2(C-7, quinolin-3-one ring), 55.6(-OCH3), 55.7(-OCH3), 111.2, 112.4, 123.6, 127.6, 128.1, 128.2, 128.5, 128.7, 128.8, 129.5, 129.6, 129.7, 129.9, 132.4, 134.6, 134.5, 135.6, 136.6, 138.8, 149.5, 154.5, 159.2, 160.1, 160.5 (C=O, pyrimidinone ring), 193.5 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 576; Anal. Calcd for C34H26ClN3O4 : C, 70.89; H, 4.55; N, 7.29. Found: C, 70.81; H, 4.93; N, 7.38.
6-Methoxy-4-[1-(4-methoxyphenyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl]-4-methyl-2-phenyl-4H-quinolin-3-one 6j.
Yellow solid; mp 152-153 0C; IR (KBr) νmax 1665, 1687 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 3.86(s, 3H, OCH3), 3.87(s, 3H, OCH3), 6.67-7.99 (m, 17H, ArH), 8.31(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.6(-CH3), 51.3(C-7, quinolin-3-one ring), 55.5(-OCH3), 55.7(-OCH3), 111.3, 112.3, 123.5, 127.7, 128.2, 128.4, 128.7, 128.8, 128.9, 129.6, 129.7, 129.8, 129.9, 132.4, 134.5, 134.6, 135.8, 136.7, 138.9, 149.3, 154.4, 159.3, 160.0, 160.3 (C=O, pyrimidinone ring), 193.6 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 542; Anal. Calcd for C34H27N3O4 : C, 75.40; H, 5.02; N, 7.76. Found: C, 75.54; H, 4.99; N, 7.81.

6-Methoxy-2-(4-methoxyphenyl)-4-[1-(4-methoxy-phenyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl]- 4-methyl-4H-quinolin-3-one 6k.
Yellow solid; mp 128-129 0C; IR (KBr) νmax 1665, 1689 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.73(s, 3H, CH3), 3.87(s, 6H, OCH3), 3.88(s, 3H, OCH3), 6.67-7.98 (m, 17H, ArH), 8.34(s, 1H olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.7(-CH3), 51.2(C-7, quinolin-3-one ring), 55.6(-OCH3), 55.6(-OCH3), 55.7(-OCH3), 111.4, 112.5, 123.4, 127.6, 128.3, 128.4, 128.5, 128.6, 128.7, 129.7, 129.8, 129.9, 130.1, 132.2, 134.4, 134.5, 135.6, 136.5, 138.7, 149.4, 154.4, 159.1, 160.1, 160.4 (C=O, pyrimidinone ring), 193.6 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 572; Anal. Calcd for C35H29N3O5 : C, 73.54; H, 5.11; N, 7.35. Found: C, 73.78; H, 5.25; N, 7.32.

6-Methoxy-4-[1-(4-methoxyphenyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-yl]-4-methyl-2-p-tolyl-4H- quinolin-3-one 6l.
Yellow solid; mp 130-131 0C; IR (KBr) νmax 1666, 1689 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.71(s, 3H, CH3), 3.86(s, 3H, OCH3), 3.88(s, 3H, OCH3), 6.65-7.96 (m, 17H, ArH), 8.35(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 24.8(-CH3), 51.1(C-7, quinolin-3-one ring), 55.5(-OCH3), 55.6(-OCH3), 111.3, 112.4, 123.5, 127.7, 128.3, 128.5, 128.6, 128.7, 128.8, 129.7, 129.8, 129.9, 130.2, 132.3, 134.5, 134.6, 135.6, 136.6, 138.8, 149.5, 154.5, 159.2, 160.3, 160.5 (C=O, pyrimidinone ring), 193.5 (C=O, quinolin-3-one ring): MS m/z [M+1]+: 556; Anal. Calcd for C35H29N3O4 : C, 75.66; H, 5.26; N, 7.56. Found: C, 75.75; H, 5.32; N, 7.63.

5-[2-(4-Chlorophenyl)-6-methoxy-4-methyl-3,4-dihydroquinolin-4-yl]-2,3-diphenyl-3H-pyrimidin-4-one7a.
Yellow solid; mp 179-180 0C; IR (KBr) νmax 1668 cm-1; 1HN MR (300 MHz, CDCl3) : δ 1.87 (s, 3H, CH3), 2.35 (d, 1H, J =16.5 Hz), 3.88 (s, 3H, OCH3), 4.35(d, 1H, J = 16.5 Hz), 7.08-7.51(m, 17H, ArH), 7.95(s,1H, olefinic proton), 13CNMR (75MHz, CDCl3) :21.1(-CH3), 23.6(C-7), 38.3(-CH2-dihydroquinoline ring), 56.7(-OCH3), 111.4, 112.0, 113.4, 121.2, 124.9, 127.3, 127.8, 128.1, 128.5, 128.6, 128.9, 129.5, 129.7, 130.6, 132.2, 132.9,134.4, 136.1, 150.4, 159.0, 161.2; MS m/z [M+1]+: 532; Anal. Calcd for C33H26ClN3O2 : C, 74.50; H, 4.93; N, 7.90. Found: C, 74.84; H, 4.82; N, 7.99.

5-(6-Methoxy-4-methyl-2-phenyl-3,4-dihydro-quinolin-4-yl)-2,3-diphenyl-3H-pyrimidin-4-one 7b.
Yellow solid; mp 185-186 0C; IR (KBr) νmax 1667 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.87 (s, 3H, CH3), 2.37 (d, 1H, J =16.5 Hz), 3.89 (s, 3H, OCH3), 4.37(d, 1H, J = 16.5 Hz), 7.02-7.55(m, 18H, ArH), 7.99(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 21.4(-CH3), 23.6(C-7), 38.5(-CH2-dihydroquinoline ring), 56.6(-OCH3), 111.6, 112.1, 113.3, 121.4, 124.8, 127.5, 127.8, 128.2, 128.5, 128.6, 128.8, 129.6, 129.9, 130.5, 132.3, 132.8, 134.8, 136.3, 150.1, 159.2, 161.1; MS m/z [M+1]+: 498; Anal. Calcd for C33H27N3O2 : C, 79.66; H, 5.47; N, 8.44. Found: C, 79.82; H, 5.55; N, 8.49.

5-[6-Methoxy-2-(4-methoxyphenyl)-4-methyl-3,4-dihydroquinolin-4-yl]-2,3-diphenyl-3H-pyrimidin-4- one 7c.
Yellow solid; mp 188-189 0C; IR (KBr) νmax 1668 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.88 (s, 3H, CH3), 2.34 (d, 1H, J =16.4 Hz), 3.84 (s, 6H, OCH3), 4.36(d, 1H, J = 16.4 Hz), 7.03-7.53(m, 17H, ArH), 7.98(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 21.4(-CH3), 23.6(C-7), 38.5(-CH2-dihydroquinoline ring), 56.5(-OCH3), 56.6(-OCH3), 111.3, 112.4, 113.7, 121.3, 124.7, 127.6, 127.7, 128.3, 128.4, 128.5, 128.8, 129.2, 129.7, 130.4, 132.4, 132.7, 134.5, 136.4, 150.0, 159.4, 161.3; MS m/z [M+1]+: 528; Anal. Calcd for C34H29N3O3 : C, 77.40; H, 5.54; N, 7.90. Found: C, 77.50; H, 5.45; N, 7.85.

5-[2-(4-Chlorophenyl)-6-methoxy-4-methyl-3,4-dihydroquinolin-4-yl]-2-phenyl-3-p-tolyl-3H-pyrimidin-4-one 7d.
Yellow solid; mp 199-200 0C; IR (KBr) νmax 1668 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.89(s, 3H, CH3), 2.33(s, 3H, CH3), 2.36 (d, 1H, J =16.5 Hz), 3.89 (s, 3H, OCH3), 4.34(d, 1H, J = 16.5 Hz), 6.99-7.48(m, 16H, ArH), 8.01(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.8(-CH3), 21.4(-CH3), 23.5(C-7), 38.5(-CH2-dihydroquinoline ring), 56.8(-OCH3), 111.6, 112.5, 113.5, 121.4, 124.6, 127.5, 127.7, 128.3, 128.4, 128.6, 128.7, 129.1, 129.3, 130.2, 132.3, 132.8, 134.7, 136.7, 151.2, 159.2, 161.1; MS m/z [M+1]+: 546; Anal. Calcd for C34H28 ClN3O2 : C, 74.78; H, 5.17; N, 6.49. Found: C, 74.70; H, 5.29; N, 6.44.

5-(6-Methoxy-4-methyl-2-phenyl-3,4-dihydro-quinolin-4-yl)-2-phenyl-3-p-tolyl-3H-pyrimidin-4-one 7e.
Yellow solid; mp 190-191 0C; IR (KBr) νmax 1665 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.87(s, 3H, CH3), 2.31(s, 3H, CH3), 2.35 (d, 1H, J =16.5 Hz), 3.85 (s, 3H, OCH3), 4.36(d, 1H, J = 16.5 Hz), 7.02-7.50(m, 17H, ArH), 7.99(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.7(-CH3), 21.2(-CH3), 23.6(C-7), 38.3(-CH2-dihydroquinoline ring), 56.6(-OCH3), 110.9, 112.2, 113.3, 121.2, 124.5, 127.4, 127.6, 128.2, 128.4, 128.5, 128.6, 129.2, 129.4, 130.3, 132.2, 132.6, 134.7, 136.6, 151.1, 159.3, 160.8; MS m/z [M+1]+: 512; Anal. Calcd for C34H29N3O2 : C, 79.82; H, 5.71; N, 8.21. Found: C, 79.79; H, 5.89; N, 8.27.

5-[6-Methoxy-2-(4-methoxyphenyl)-4-methyl-3,4-dihydroquinolin-4-yl]-2-phenyl-3-p-tolyl-3H- pyrimidin-4-one 7f.
Yellow solid; mp 195-196 0C; IR (KBr) νmax 1667 cm-1; 1H NMR (300 MHz, CDCl3) : δ 1.88(s, 3H, CH3), 2.31(s, 3H, CH3), 2.34 (d, 1H, J =16.4 Hz), 3.86 (s, 6H, OCH3), 4.36(d, 1H, J = 16.4 Hz), 7.02-7.52(m, 16H, ArH), 8.01(s, 1H, olefinic proton), 13C NMR (75 MHz, CDCl3) : 19.9(-CH3), 21.5(-CH3), 23.7(C-7), 38.8(-CH2-dihydroquinoline ring), 56.6(-OCH3), 56.7(-OCH3), 111.2, 112.5, 113.6, 121.7, 124.8, 127.5, 127.7, 128.2, 128.3, 128.5, 128.8, 129.2, 129.3, 130.3, 132.4, 132.7, 134.6, 136.8, 151.1, 159.5, 161.0; MS m/z [M+1]+: 542; Anal. Calcd for C35H31N3O3 : C, 77.61; H, 5.77; N, 7.66. Found: C, 77.77; H, 5.72; N, 7.47.

ACKNOWLEDGEMENTS
We are thankful to Professor Takao Saito, University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan for providing 600 MHz NMR spectra. NMR facility of Department of Chemistry, GNDU, Amritsar funded by Department of Science and Technology, Govt. of India, is gratefully acknowledged.

References

1. S. M. Weinreb, B. M. Trost, and I. Fleming, Comprehensive Organic Synthesis. Eds.; Pergamon: Oxford. 1991; Vol. 5, 401–449; (b) D. L. Boger and S. M. Weinreb, Hetero Diels–Alder Methodology in Organic Synthesis. Academic: San Diego, 1987, Chapters 2 and 9.
2. (a) S. Kobayashi, H. Ishitani, and S. Nagayama, Chem. Lett., 1995, 24, 423; CrossRef (b) H. Ishitani and S. Kobayashi, Tetrahedron Lett., 1996, 37, 7357; CrossRef (c) S. Kobayashi, M. Araki, H. Ishitani, S. Nagayama, and I. Hachiya, Synlett, 1995, 233; CrossRef (d) S. Kobayashi, H. Ishitani, and S. Nagayama, Synthesis, 1995, 1195. CrossRef
3. (a) H. J. Roth and H. Fenner, In Arzneistoffe, 3rd ed.; Deutscher Apotheker Verlag: Stuttgart. 2000; pp. 51–114; (b) N. Yamada, S. Kadowaki, K. Takahashi, and K. Umezu, Biochem. Pharmacol., 1992, 44, 1211; CrossRef (c) K. Faber, H. Stueckler, and T. Kappe, J. Heterocycl. Chem., 1984, 21, 1177; CrossRef (d) J. V. Johnson, B. S. Rauckmann, D. P. Baccanari, and B. Roth, J. Med. Chem., 1989, 32, 1942; CrossRef (e) I. Nesterova, L. M. Alekseeva, A. L. Mndreeva, S. M. Golovira, and V. G. Granic, Khim. Farm. Zh., 1995, 29, 31; (f) K. J. Rajendra Prasad and M. Sekar, J. Nat. Prod., 1998, 61, 294; CrossRef (g) S. E. Hagen, J. M. Domagala, C. L. Heifetz, J. P. Sanchez, and M. Solomon, J. Med. Chem., 1990, 33, 849; CrossRef (h) M. Hadjeri, E.-L. Peiller, C. Beney, N. Deka, M. A. Lawson, C. Dumontet, and A. Boumendjel, J. Med. Chem., 2004, 47, 4964; CrossRef (i) S. C. Kuo, H. Lee, Z. Juang, J. P. Lin, Y. T. Wu, T. S. Cheng, J. J. Lednicer, D. Paull, K. D. Lin, C. M. Hamel, and E. Lee, J. Med. Chem., 1993, 36, 1146. CrossRef
4. (a) L. F. Tietze and G. Kettschau, Top. Curr. Chem., 1997, 189, 1; CrossRef (b) S. Kobayashi, Eur. J. Org. Chem., 1999, 15; CrossRef (c) M. Panunzio and P. Zarantonello, Org. Process Res. Dev., 1988, 2, 49; CrossRef (d) D. Enders and O. Meyer, Liebigs Ann. Chem., 1996, 1023; (e) H. Waldmann, Organic Synthesis Highlights II. H. Waldman, VCH: New York, NY, 1995; pp. 37-47; (f) H. Waldmann, Synthesis, 1994, 535; CrossRef (g) H. Waldmann and M. Braun, Gazz. Chim. Ital., 1991, 121, 277; (h) H. Waldmann, Synlett, 1995, 133; CrossRef (i) J. Barluenga, J. Joglar, J. F. Gonzalez, and S. Fustero, Synlett, 1990, 129; CrossRef (j) D. T. Parker, Organic Synthesis in Water; P. A. Grieco, Ed.; Blackie Academic and Professional: London, 1998; 2, pp. 47-81; (k) J. Barluenga and M. Tomas, Adv. Heterocycl. Chem., 1993, 57, 1; CrossRef (l) P. Boonra, F. C. Oslen, and T. Oh, Tetrahedron, 2001, 54, 6099. CrossRef
5. For recent example on Imino DA reaction see: (a) L. C. Da Silva-Filho, V. L. Júnior, M. G. Constantino, and G. V. J. Da Silva, Synthesis, 2008, 2527; CrossRef (b) R. Nagarajan, S. Chitra, and P. T. Perumal, Tetrahedron, 2001, 57, 3419; CrossRef (c) G. Babu and P. T. Perumal, Tetrahedron, 1999, 55, 4793; CrossRef (d) G. Babu and P. T. Perumal, Tetrahedron Lett., 1998, 39, 3225; CrossRef (e) G. Babu and P. T. Perumal, Tetrahedron., 1998, 54, 1627; CrossRef (f) G. Babu and P. T. Perumal, Tetrahedron Lett., 1997, 38, 5025. CrossRef
6. (a) C. Mohan, G. Bhargava, A. P. S. Pannu, and M. P. Mahajan, Tetrahedron Lett., 2007, 48, 1711; CrossRef (b) G. Bhargava, C. Mohan, and M. P. Mahajan, Tetrahedron, 2008, 64, 3017; CrossRef (c) G. Bhargava, V. Kumar, and M. P. Mahajan, Tetrahedron Lett., 2007, 48, 2365; CrossRef (d) G. Bhargava, T. Saito, and M. P. Mahajan, Synlett, 2008, 983. CrossRef
7. (a) D. C. Rowley, M. S. T. Hansen, D. Rhodes, C. A. Striffer, H. Ni, J. A. McCammon, F. D. Bushman, and W. Fenical, Bioorg. Med. Chem., 2002, 10, 3619; CrossRef (b) P. Molina, E. Aller, A. Lorenzo, P. Lopez-Cremades, I. Rioja, A. Ubeda, M. C. Terencio, and M. J. Alcaraz, J. Med. Chem., 2001, 44, 1011; CrossRef (c) A. Kumar, S. Sinha, and P. M. S. Chauhan, Bioorg. Med. Chem. Lett., 2002, 12, 667; CrossRef (d) J. B. Bher, T. Gourlain, A. Helimi and G. Guillerm, Bioorg. Med. Chem. Lett., 2003, 13, 1713; CrossRef (e) H. P. De Koning, M. I. Al-Salabi, A. M. Cohen, G. H. Coombs, and J. M. Wastling, Int. J. Parasitol., 2003, 33, 821; CrossRef (f) H. M. Hosni, W. M. Basyouni, and H. A. El-Nahas, J. Chem. Res., 1999, 646; (g) M. Botta, F. Occhionero, R. Nicoletti, P. Mastromarino, C. Conti, M. Margini, and J. Saladino, Bioorg. Med. Chem., 1999, 9, 1925. CrossRef
8. (a) S. Kobayashi and S. Nagayama, J. Am. Chem. Soc., 1996, 118, 8977; CrossRef (b) S. Kobayashi, H. Ishitani, and S. Nagayama, Chem. Lett., 1995, 24, 423. CrossRef
9. (a) C. Massimo, E. Francesco, G. Salvatore, M. M. Carla, and R. Ornelio, Org. Lett., 2005, 7, 1331; CrossRef (b) M. D. Garcia, A. J. Wilson, D. P. G. Emmerson, and P. R. Jenkins, Chem. Commun., 2006, 2586. CrossRef
10. K. K. Laal, M. Hekert, C. Brad, A. Bhatt, and T. David, J. Chem. Soc., Perkin Trans. 1, 2001, 578. CrossRef