Copper-catalysed heteroannulation with alkynes: A general and highly regio- and stereoselective method for the synthesis of (E)-2-(2-arylvinyl) quinazolinones

Article abstract of DOI:10.1016/S0040-4020(01)00637-8

A highly regio- and stereoselective procedure for the synthesis of 2-substituted-1,2,3,4-tetrahydroquinazolinones through a two-step procedure, e.g. (i) palladium-copper catalysed C-arylation of terminal alkynes and (ii) copper-catalysed cyclisation of di

Full text of DOI:10.1016/S0040-4020(01)00637-8

TETRAHEDRON
Pergamon
Tetrahedron 57 *2001) 6833±6842
Copper-catalysed heteroannulation with alkynes: a general and
highly regio- and stereoselective method for the synthesis of
ꢀE)-2-ꢀ2-arylvinyl) quinazolinones
Nitya G. Kundup and Gopeswar Chaudhuri
Department of Organic Chemistry, Indian Association for Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 2 March 2001; revised 14 May 2001; accepted 7 June 2001
AbstractÐAhighly regio- and stereoselective procedure for the synthesis of 2-substituted-1,2,3,4-tetrahydroquinazolinones through a two-
step procedure, e.g. *i) palladium±copper catalysed C-arylation of terminal alkynes and *ii) copper-catalysed cyclisation of disubstituted
alkynes, is described. 2-*N-Alkyl-N-prop-20-ynyl)amino-N0- p-tolyl benzamides 5a and 5b reacted with aryl iodides 2 in the presence of
*Ph3P)2PdCl2 *2.5 mol%), CuI *5 mol%), Et3N *5 equiv.) in CH3CN at rt for 16 h to yield the disubstituted alkynes 6±18 which could then be
cyclised with CuI *20 mol%), K2CO3 *2.5 equiv.), Bu4NBr *1 equiv.) in CH3CN at 808C for 16±24 h to yield 1-methyl *benzyl)-*E)-2-*2-
arylvinyl)-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-4-ones 19±31 in good yields. Only in a few cases, the benzodiazepinones 32±34 could be
obtained in poor yield. The synthesis of novel uracil derivatives 35 and 36 is also described. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
The quinazoline1 structure has been the integral part of
many naturally occurring and biologically active
compounds. For example, febrifugine *I) and isofebriguine
were isolated as the active principles2±4 of the roots of
Dichroa febrifuga Lour *Chinese name: Chang Shan)
which have been used effectively against malaria fever in
China for centuries. Recently a new type of febrifugine
derivative has been reported5 which showed high activity
against P. falciparum malaria in vitro and was equally effec-
tive against P. berghei in vivo as the clinically used drug
chloroquine. Similarly, quinazoline containing structures
have been known as tyrosine kinase inhibitors,6 dihydro-
folate reductase *DHFR) inhibitors,7 tubulin polymerisation
inhibitors8 *II) and tumour necrosis factors.9 Thus, many
Palladium-catalysed reactions17 have been of immense
quinazoline containing molecules have been developed as
anticonvulsants,10 antihypertensives,11 antidiabetics,12 and
as antitumour,13 antimicrobial14 and antibacterial15 agents.
In view of the importance of quinazolines and their deriva-
tives, many classical methods for the synthesis of quinazo-
lines and quinazolinones have been reported in the
literature.1,16
signi®cance in both carboannulation18 and heteroannula-
tion19 processes. We have utilised palladium±copper
catalysed reactions20 of terminal alkynes for the synthesis
of various benzofused heterocyclic compounds.21 Recently,
we have described22 a highly regio- and stereoselective
procedure for the synthesis of *Z)-3-arylidene-2,3-dihydro-
5H-1,4-benzodioxepin-5-ones 4a and *Z)-3-arylidene-2,3-
dihydro-5H-4,1-benzoxazepin-5-ones
4b
through
palladium±copper catalysed reactions of 1a and 1b with
aryl iodides 2, where in the ®nal step, a copper-catalysed
exo-dig attack by a carboxylate ion on the disubstituted
alkynes 3a and 3b took place *Scheme 1).
Keywords: quinazolinones; disubstituted alkynes; palladium±copper
catalysis; copper-catalysed heteroannulation; terminal alkynes.
Corresponding author. Tel.: 191-33-473-4971; fax: 191-33-473-2805;
e-mail: ocbn@mahendra.iacs.res.in
p
In this article we describe a general palladium and
copper catalysed procedure for the synthesis of
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020*01)00637-8

6834
N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
Scheme 1.
2-substituted-1,2,3,4-tetrahydroquinazolin-4-ones23 where
in contrast to the expected benzodiazepinone derivatives,
the tetrahydroquinazolin-4-ones were formed predomi-
nently.
disubstituted alkynes. It is to be noticed that in the reaction
of the benzamides 5a or 5b with the aryl iodides 2, the
disubstituted alkynes were the sole products. In contrast
to the formation of the 1,4-benzodioxans21g,h under
palladium±copper catalysed reaction where C-arylation
and cyclisation took place in one step, in this case no cyclic
products were formed in one-step under palladium±copper
catalysed conditions.
2. Results and discussion
2.1. Synthesis of disubstituted alkynes
2.2. Synthesis of the quinazolinones
2-*N-Methyl-N-prop-20-ynyl)amino-N0-p-tolylbenzamide
5a or, 2-*N-benzyl-N-prop-20-ynyl)amino-N0-p-tolylbenza-
mide 5b reacted with the aryl iodides 2 in the presence of
bis*triphenylphosphine)palladium*II) chloride *2.5 mol%),
cuprous iodide *5 mol%), triethylamine *5 equiv.) in aceto-
nitrile at rt for 16 h to yield the disubstituted alkynes *6±18)
in good yields. Both the palladium-catalyst and the cuprous
iodide as co-catalyst were found to be essential for the
C-arylation of the terminal alkynes. Also, triethylamine
was found to be the base of choice. However, triethylamine
alone could not act as the solvent since the benzamides 5a
and 5b were found to be sparingly soluble in triethylamine.
The use of CH3CN as solvent facilitated the formation of the
The disubstituted alkynes 6±18 could, however, be cyclised
with cuprous iodide *20 mol%) in the presence of potassium
carbonate *2.5 equiv.) and tetrabutyl ammonium bromide
*1 equiv.) by heating in acetonitrile at 808C for 16±24 h.
In most cases *Table 1, entries 1±8, 11 and 13), the *E)-2-
*arylvinyl)quinazolines 19±26, 29 and 31 were formed in a
highly regio- and stereoselective manner. Only in a few
cases *entries 9, 10 and 12) were small amounts *7±10%)
of the benzodiazepinones 32±34 formed *Scheme 2).
The cuprous iodide was found to be the most effective
catalyst for the cyclisation process. The use of the
Table 1. Palladium±copper catalysed reactions of 2-*N-alkyl-N-prop-20-ynyl) amino-N0-p-tolyl benzamides *5a, 5b) with aryl iodides *2) leading to disub-
stituted alkynes *6±18) and their subsequent cyclisation to quinazolin-4-ones *19±31)
Entry
N±R
Aryl iodides *Ar)
Disubstituted alkynes *%)a
Quinazolinones *%)b
Benzodiazepinones *%)b
1
2
3
4
5
6
7
5a *Me)
5a *Me)
5a *Me)
5a *Me)
5a *Me)
5a *Me)
5a *Me)
2a *Ph)
6 *84)
7 *76)
8 *70)
9 *67)
10 *90)
11 *75)
12 *79)
19 *60)
20 *67)
21 *35)
22 *31)
23 *69)
24 *61)
25 *65)
2b *C6H4Me-o)
2c *C6H4OMe-o)
2d *C6H4OMe-p)
2e *C6H4CO2Me-o)
2f *2-Thienyl)
2g *2,4-Dimethoxy-
pyrimidin-5-yl
2b *C6H4Me-o)
2h *C6H4Me-p)
2I *C6H4Cl-m)
2e *C6H4CO2Me-o)
2f *2-Thienyl)
8
9
10
11
12
13
5b *Bn)
5b *Bn)
5b *Bn)
5b *Bn)
5b *Bn)
5b *Bn)
13 *72)
14 *65)
15 *67)
16 *89)
17 *73)
18 *91)
26 *63)
27 *59)
28 *60)
29 *61)
30 *67)
31 *62)
32 *8)
33 *7)
34 *10)
2g *2,4-Dimethoxy-
pyrimidin-5-yl)
a
Yields are based on aryl iodides.
Yields are based on the corresponding disubstituted alkynes.
b

N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
6835
Scheme 2.
phase-transfer catalyst, e.g. n-Bu4NBr, in the cyclisation
reaction improved the yield of the quinazolinones consider-
ably. When Pd*OAc)2 was used instead of CuI, a mixture of
*E) and *Z) isomers of the quinazolinones was obtained.
Potassium carbonate was found to be essential for the cycli-
sation process. The use of triethylamine alone did not lead to
any cyclisation. When NaOEt in ethanol or NaH in THF was
used as the cyclising agent, a mixture of *E)- and *Z)-
isomers of the quinazolinones were obtained. Again in the
cyclisation process, the use of CH3CN as a solvent led to
cleaner cyclic products. The use of DMF as a solvent led to
poorer yields due to formation of much coloured materials.
the double bond follows from the coupling constant values
of 15.6±15.9 Hz for the vinylic protons.
The structures of the benzodiazepinones 32±34 were estab-
1
lished on the basis of their H NMR, 13C NMR and 13C
DEPT-135 experiments. In H NMR, the presence of a
1
vinylic proton *exocyclicˆCH) was seen as a singlet at d
6.23±6.62. Also, two ±CH2 groups were seen as two distinct
singlets at d 4.33±4.37 and 3.86±3.94, respectively. This
was con®rmed by 13C DEPT-135 experiments where two
inverted peaks were observed at d 55.9±56.07 and 63.10±
64.17 respectively. The Z-stereochemistry of the benzo-
3
3
diazepinones follows from JCH experimentsÐthe JCH
values of 3.75 and 4.25 Hz were observed for compounds
32 and 34, respectively.24
2.3. Characterisation of products
The quinazolinones 19±31 gave satisfactory analytical, IR,
1H and 13C NMR data. The absence of the ±NH± peak in IR
and 1H NMR indicated the formation of the cyclic products.
The identi®cation of the cyclic products as the quinazoli-
nones 19±31 follows from *i) the absence of a ring methyl-
2.4. Mechanism
Mechanistically, the formation of the disubstituted alkynes
6±18 is easily explained by the Sonogashira±Tohda±
Hagihara coupling20a which involved *i) the generation of
Pd0 from *Ph3P)2PdCl2, *ii) formation of ArPdX from ArX
and Pd0, *iii) transmetallation of the ArPdX with Cu-salt of
the acetylenic compounds 5a and 5b and *iv) reductive
elimination of Pd0 leading to the disubstituted alkynes.25
1
ene peak for compounds 19±31 both in H and 13C NMR
data, *ii) the presence of N2CH as a doublet at d 5.04±5.18
*Jˆ6.9±8.4 Hz), *iii) the presence of vCHAr as a doublet
at d 6.23±6.83 *Jˆ15.0±15.9 Hz) and *iv) the presence of
±CHvCAr as a double doublet at d 6.15±6.45 *J1ˆ15.6±
15.9 Hz and J2ˆ7.5±8.4 Hz). The E-stereochemistry around
Scheme 3.

6836
N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
Scheme 4.
In the normal cyclisation of the disubstituted alkynes, a
nucleophilic attack by the amide nitrogen on the triple
bond led to the benzodiazepinones 32±34. However, in
most of the cases, a rearrangement of 6±18 to the allenic
intermediates Atook place involving alkyne±allene
rearrangement26 in the propargyl group attached to the
nitrogen atom. Asubsequent nucleophilic attack by
the amide nitrogen on the terminal carbon *next to the
N-atom) of the allenes would result in the quinazolinones
19±31 *Scheme 3).
palladium±copper catalysed general procedure for the
synthesis of 2-substituted quinazolinones. Also, interest-
ingly, many quinazolines of biological importance are
accessible by our synthetic procedure.
4. Experimental
4.1. General
Melting points were determined on a Reichert *285980)
*Austria) melting point apparatus and are uncorrected. IR
Spectra were taken on a FTIR-8300, SHIMADZU instru-
ment. 1H NMR spectra were recorded on a Varian EM-360
and a Bruker DPX-300 spectrometer for samples as indi-
cated with tetramethylsilane as internal references. 13C
NMR spectra *75 MHz) were obtained on a Bruker DPX-
300 spectrometer. Chemical shifts are reported in d unit
*parts per milion); J values given in Hz; splitting patterns
are designated as follows: s, singlet; d, doublet, t, triplet, q,
quartet, dd, double doublet, m, multiplet, br, broad. Analy-
tical thin-layer chromatography *TLC) was performed on
precoated 0.2 mm silica gel 60F-254 *E. Merck) and the
spots were visualised with UV light. Column chromato-
graphy was done on silica gel *60±120 mesh) or neutral
alumina. Elemental analyses *C,H,N) were carried out on
Perkin±Elmer 240C Analyser. Propargyl alcohol, phos-
phorus tribromide and tetrabutyl ammonium bromide were
commercially available.
2.5. Scope
Many 2-arylvinylquinazolines have shown interesting
biological properties.
Our method is amply suitable for the synthesis of such
compounds. Also, the compounds 19±31 which are
structurally similar to the existing biologically active
compound II could demonstrate interesting biological and
pharmacological properties. Of particular interest are the
pyrimidine derivatives, e.g. 1-methyl-*E)-2-[2-*2,4-
dimethoxypyrimidin-5-yl)vinyl]-3-p-tolyl-1,2,3,4-tetrahydro-
quinazolin-4-one 25 and 1-benzyl-*E)-2-[2-*2,4-dimethoxy-
pyrimidin-5-yl)vinyl]-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-
4-one 31 which could be demethylated with TMSCl and NaI
in CH3CN to 1-methyl-*E)-2-[2-*uracil-5-yl)vinyl]-3-p-tolyl-
1,2,3,4-tetrahydroquinazolin-4-one 35 and 1-benzyl-*E)-2-[2-
*uracil-5-yl)vinyl]-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-
4-one 36, respectively, novel 5-substituted uracil derivatives
*Scheme 4).
Bis*triphenylphosphine)palladium*II)chloride, Pd*OAc)2
and copper iodide were purchased from Aldrich Chemical
Co., Milwaukee, Wisconsin, U.S.A.
Since 5-substituted uracils have shown exceedingly inter-
esting antiviral and anticancer activities,27 compounds 35
and 36 are of great biological curiosity.
The aryl iodides *2b±e, 2h, 2i) were prepared according to
the procedures given for the synthesis of iodobenzene28
*2a). 2-Iodothiophene29 *2f) and 5-iodo-2,4-dimethoxy-
pyrimidine30 *2g) were synthesised according to known
procedures.
3. Conclusion
In this paper, we have described a highly general and facile
method for the synthesis of 2-substituted quinazolin-4-ones.
The method involves *i) an ef®cient palladium±copper cata-
lysed procedure for the synthesis of disubstituted alkynes
and *ii) a highly regio- and stereoselective copper-catalysed
cyclisation of the alkynes to 1,2,3,4-tetrahydroquinazolin-4-
ones. The process is characterised by the easy availability of
inexpensive starting materials, relatively mild reaction
conditions and work-up procedures and fairly good yields
of the products. We believe this is the ®rst reported
4.1.1. Synthesis of 2-ꢀN-methyl-N-prop-20-ynyl)amino-
benzoic acid. Amixture of methyl anthranilate *5 g,
33.07 mmol) and anhydrous potassium carbonate *4.56 g,
33.07 mmol) in dry DMF *20 mL) was stirred for 8 h at rt
under a N2 atmosphere. Propargyl bromide *4.72 g,
39.68 mmol) in dry DMF *10 mL) was then added slowly
over 30 min. The whole mixture was heated at 808C for 48 h
with constant stirring under a N2 atmosphere. DMF was
removed from the reaction mixture under reduced pressure

N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
6837
and the residue was extracted with chloroform *3£50 mL)
and distilled water *50 mL). The chloroform extract was
washed with water *2£50 mL) and dried over anhydrous
sodium sulfate. After removal of solvent, the residue was
puri®ed by column chromatography on silica gel using 1:1
chloroform±light petroleum ether *bp 60±808C) as eluent to
yield methyl 2-*N-prop-20-ynyl)aminobenzoate, yield
4.43 g, *71%); mp 63±658C; IR: nmax *KBr) 3369, 3284,
solution, p-toluidine *1.7 g, 15.9 mmol) in benzene
*15 mL) was added and the reaction mixture was stirred at
rt for 16 h under N2-atmosphere. After usual work-up and
puri®cation on silica gel, using chloroform±light petroleum
ether *3:1) as eluent, 2-*N-methyl-N-prop-20-ynyl)amino-
N0-p-tolylbenzamide was obtained as a colourless oil,
yield 1.8 g *61%); IR: nmax *neat) 3290, 3236, 2116, 1666,
1
1595 cm21; H NMR *60 MHz, CCl4) d 2.3 *s, 3H, Ar±
1
1686 cm21; H NMR *60 MHz, CCl4) d 2.03 *t, Jˆ2.0 Hz,
CH3), 2.33 *t, Jˆ2.0 Hz, 1H, CuCH), 3.0 *s, 3H,
±NCH3), 3.82 *d, Jˆ2.0 Hz, 2H, ±NCH2), 6.92±7.66 *m,
7H, ArH), 8.13±8.33 *m, 1H, ArH), 11.80 *s, br, 1H,
±CONH). Anal. Calcd for C18H18N2O: C, 77.66; H, 6.51;
N, 10.06. Found: C, 77.72; H, 6.54; N, 10.14.
1H, CuCH), 3.66 *s, 3H, ±CO2Me), 3.79±3.95 *dd,
Jˆ4.0 Hz, 2H, ±NCH2), 6.36±6.69 *m, 3H, ArH, NH),
7.09±7.42 *m, 1H, ArH), 7.66±7.89 *m, 1H, ArH). Anal.
Calcd for C11H11NO2: C, 69.82; H, 5.86; N, 7.4. Found: C,
69.69; H, 5.68; N, 7.29.
4.1.3. Synthesis of 2-ꢀN-benzyl-N-prop-20-ynyl)amino-
N0-p-tolyl benzamide 5b. 2-*N-Benzyl-N-prop-20-ynyl)-
amino-N0-p-tolyl benzamide 5b was synthesised from
2-*N-benzyl-N-prop-20-ynyl)aminobenzoic acid by follow-
ing the procedure used for the synthesis of compound 5a.
Yield 65%; colourless crystalline solid; mp 1258C; IR: nmax
Amixture of methyl 2-* N-prop-20-ynyl)aminobenzoate
*4 g, 21.14 mmol) and anhydrous potassium carbonate
*2.92 g, 21.14 mmol) in dry DMF *15 mL) was stirred for
8 h at rt under N2 atmosphere. Methyl iodide *9 g,
63.42 mmol) was then added slowly to it under ice-cold
condition over 20 min. The whole reaction mixture was
heated at 608C for 24 h under a N2 atmosphere. The residue
obtained after removal of DMF under reduced pressure was
extracted with chloroform *3£40 mL) and water *50 mL).
The combined chloroform layers were washed with water
*2£50 mL) and dried over anhydrous sodium sulfate. After
the removal of the solvent, the residue was puri®ed by
column chromatography over silica gel using 3:1 chloro-
form±petroleum ether as eluent. Methyl 2-*N-methyl-N-
prop-20-ynyl)aminobenzoate was obtained as a colourless
*KBr) 3294, 3230, 2106, 1666, 1595 cm21 1H NMR
;
*60 MHz, CCl4) d 2.31 *s, 3H, Ar±CH3), 2.32 *t,
Jˆ2.0 Hz, 1H, uCH), 3.69 *d, Jˆ2.0 Hz, 2H, ±NCH2),
4.36 *s, 2H, ±NCH2Ph), 6.89±7.56 *m, 12H, Ar±H),
8.19±8.46 *m, 1H, ArH), 11.5 *s, br, 1H, ±CONH). Anal.
Calcd for C24H22N2O: C, 81.32; H, 6.25; N, 7.90. Found: C,
81.30; H, 6.09; N, 7.71.
4.2. General procedure for the synthesis of 6±18
oil, yield 3.1 g *72%). IR: nmax *neat) 3280, 1720 cm21
;
Amixture of aromatic iodocompounds 2, *Ph3P)2PdCl2
*2.5 mol%), CuI *5 mol%), Et3N *5 equiv.) was stirred in
acetonitrile at rt for 30 min under an argon atmosphere.
The acetylenic compound 5a or 5b *1 equiv.) dissolved in
acetonitrile was added slowly to it and the reaction mixture
was allowed to stir at rt for a further period of 16 h. The
residue obtained after removal of CH3CN was taken up in
chloroform. The CHCl3 layer was washed with water, dried
over anhydrous sodium sulphate and was puri®ed by
column chromatography on silica gel *60±120 mesh)
using chloroform±light petroleum *3:1) as eluent to yield
the disubstituted alkynes *6±18) in excellent yields
*65±91%).
1H NMR *60 MHz, CCl4) d 2.13 *t, Jˆ1.98 Hz, 1H,
CuCH), 2.82 *s, 3H, ±NCH3), 3.80 *s, 3H, ±CO2Me),
3.82 *d, Jˆ2.0 Hz, 2H, ±NCH2), 6.66±7.33 *m, 3H, ArH),
7.50±7.70 *m, 1H, ArH). Anal. Calcd for C12H13NO2: C,
70.91; H, 6.44; N, 6.89. Found: C, 70.93; H, 6.50; N, 6.95.
Potassium hydroxide *1.40 g, 25.08 mmol) dissolved in
water *7 mL) was added dropwise to a methanolic solution
*20 mL) of methyl 2-*N-methyl-N-prop-20-ynyl)amino-
benzoate *2.55 g, 12.54 mmol) with constant stirring. This
was stirred at rt for 24 h. The residue obtained after the
removal of methanol was neutralised with dil. HCl and
worked-up with chloroform *3£40 mL) and water
*50 mL). The solid residue obtained after the removal of
chloroform was crystallised from petroleum ether *bp 60±
4.2.1. 2-[N-Methyl-N-ꢀ30-phenyl-prop-20-ynyl)amino]-
N0-p-tolyl benzamide 6. Colourless sticky oil; IR: nmax
808C)±chloroform.
benzoic acid was obtained as a white crystalline solid,
yield 2.14 g *90%); mp 1078C; IR nmax *KBr) 3295,
2-*N-Methyl-N-prop-20-ynyl)amino-
1
*neat) 3163, 2223, 1667, 1600 cm21; H NMR *60 MHz,
CCl4) d 2.26 *s, 3H, ArCH3), 2.92 *s, 3H, NCH3), 3.90 *s,
2H, ±NCH2), 6.82±7.66 *m, 12H, ArH), 8.06±8.33 *m, 1H,
ArH), 11.66 *s, 1H, ±CONH). Anal. Calcd for C24H22N2O:
C, 81.32; H, 6.25; N, 7.90. Found: C, 81.20; H, 6.16; N, 7.69.
1
1690 cm21; H NMR *60 MHz, CCl4) d 2.20 *t, Jˆ2.0 Hz,
1H, CuCH), 2.85 *s, 3H, ±NCH3), 3.85 *d, Jˆ2.0 Hz, 2H,
±NCH2), 6.68±7.35 *m, 3H, ArH), 7.51±7.72 *m, 1H, ArH),
10.18 *s, br, 1H, ±CO2H). Anal. Calcd for C11H11NO2: C,
69.82; H, 5.86; N, 7.40. Found: C, 69.80; H, 5.79; N, 7.38.
4.2.2. 2-{N-Methyl-N-[30-ꢀo-methylphenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 7. Colourless sticky oil; IR:
nmax *neat) 3165, 2233, 1668, 1595 cm21
;
1H NMR
4.1.2. Synthesis of 2-ꢀN-methyl-N-prop-20-ynyl)amino-
N0-p-tolyl benzamide 5a. 2-*N-Methyl-N-prop-20-ynyl)a-
minobenzoic acid *2 g, 10.6 mmol) was dissolved in ben-
zene *20 mL) and thionyl chloride *5 mL) and pyridine *10
drops) added. The reaction mixture was heated with stirring
at 558C for 1.5 h. The residue, obtained after removal of
solvent and excess SOCl2, was dissolved in benzene
*15 mL) and cooled in an ice-H2O bath. To the ice-cold
*60MHz, CCl4) d 2.33 *s, 6H, 2£Ar±CH3), 3.00 *s, 3H, ±
NCH3), 4.03 *s, 2H, ±NCH2), 6.89±7.69 *m, 11H, Ar±H),
8.13±8.33 *m, 1H, ArH), 11.62 *s, br, 1H, CONH). Anal.
Calcd for C25H24N2O: C, 81.48; H, 6.56; N, 7.60. Found: C,
81.27; H, 6.40; N, 7.42.
4.2.3. 2-{N-Methyl-N-[30-ꢀo-methoxyphenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 8. Colourless sticky oil; IR:

6838
N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
nmax *neat) 3168, 2230, 1665, 1600 cm21
;
1H NMR
4.2.10. 2-{N-Benzyl-N-[30-ꢀm-chlorophenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 15. Colourless solid; mp
*60 MHz, CCl4) d 2.23 *s, 3H, Ar±CH3), 2.95 *s, 3H,
±NCH3), 3.76 *s, 3H, OCH3), 3.96 *s, 2H, ±NCH2), 6.73±
7.89 *m, 11H, ArH), 8.03±8.62 *m, 1H, ArH), 11.61 *s, br,
1H, CONH). Anal. Calcd for C25H24N2O2: C, 78.09; H,
6.29; N, 7.28. Found: C, 78.05; H, 6.13; N, 7.09.
1
1418C; IR: nmax *KBr) 3165, 2227, 1659, 1593 cm21; H
NMR *60 MHz, CCl4) d 2.33 *s, 3H, Ar±CH3), 3.89 *s,
2H, ±NCH2), 4.39 *s, 2H, ±NCH2Ph), 6.92±7.66 *m, 16H,
ArH), 8.26±8.42 *m, 1H, ArH), 11.66 *s, br, 1H, ±CONH).
Anal. Calcd for C30H25N2OCl: C, 77.48; H, 5.41; N, 6.02.
Found: C, 77.46; H, 5.64; N, 6.21.
4.2.4. 2-{N-Methyl-N-[30-ꢀp-methoxyphenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 9. Colourless sticky oil; IR:
1
nmax 3170, 2228, 1665, 1600 cm21; H NMR *60 MHz,
4.2.11. 2-{N-Benzyl-N-[30-ꢀo-methoxycarbonylphenyl)-
prop-20-ynyl]amino}-N0-p-tolyl benzamide 16. Colourless
solid; mp 1158C; IR: nmax *KBr) 3161, 1728, 1664,
CCl4) d *s, 3H, Ar±CH3), 2.96 *s, 3H, ±NCH3), 3.76 *s,
3H, ±OCH3), 3.98 *s, 2H, ±NCH2), 6.78±7.88 *m, 11H,
ArH), 8.31±8.65 *m, 1H, ArH), 11.61 *s, br, 1H, CONH).
Anal. Calcd for C25H24N2O2: C, 78.09; H, 6.29; N, 7.28.
Found: C, 77.86; H, 6.08; N, 7.05.
1
1595 cm21; H NMR *60 MHz, CCl4) d 2.29 *s, 3H, Ar±
CH3), 3.90 *s, 3H, ±CO2Me), 3.92 *s, 2H, ±NCH2), 4.50 *s,
2H, ±NCH2Ph), 6.80±7.56 *m, 15H, ArH), 7.72±8.0 *m,
1H, ArH), 8.09±8.33 *m, 1H, ArH), 11.7 *s, br, 1H,
±CONH). Anal. Calcd for C32H28N2O3: C, 78.66; H, 5.77;
N, 5.73. Found: C, 78.79; H, 5.93; N, 5.94.
4.2.5. 2-{N-Methyl-N-[30-ꢀo-methoxycarbonylphenyl)-
prop-20-ynyl]amino}-N0-p-tolyl benzamide 10. Colourless
sticky oil; IR: nmax *neat) 3161, 2224, 1728, 1664,
4.2.12. 2-{N-Benzyl-N-[30-ꢀ2-thienyl)prop-20-ynyl]amino}-
N0-p-tolyl benzamide 17. Colourless solid; mp 1258C; IR:
1
1595 cm21; H NMR *60 MHz, CCl4) d 2.26 *s, 3H, Ar±
CH3), 3.09 *s, 3H, ±NCH3), 3.82 *s, 3H, ±CO2Me), 4.03 *s,
2H, ±NCH2), 6.80±7.62 *m, 10H, ArH), 7.72±8.00 *m, 1H,
ArH), 8.09±8.30 *m, 1H, ArH), 11.70 *s, br, 1H, CONH).
Anal. Calcd for C26H24N2O3: C, 75.70; H, 5.86; N, 6.79.
Found: C, 75.51; H, 5.84; N, 6.76.
;
nmax *KBr) 3163, 2224, 1663, 1595 cm21 1H NMR
*60 MHz, CCl4) d 2.29 *s, 3H, Ar±CH3), 3.89 *s, 2H,
±NCH2), 4.36 *s, 2H, ±NCH2Ph), 6.82±7.53 *m, 15H,
ArH), 8.16±8.36 *m, 1H, ArH), 11.62 *s, br, 1H,
±CONH). Anal. Calcd for C28H24N2OS: C, 77.03; H, 5.54;
N, 6.41. Found: C, 76.86; H, 5.46; N, 6.34.
4.2.6. 2-{N-Methyl-N-[30-ꢀ2-thienyl)prop-20-ynyl]amino}-
N0-p-tolyl benzamide 11. Colourless sticky oil; IR: nmax
4.2.13. 2-{N-Benzyl-N-[30-ꢀ2,4-dimethoxypyrimidin-5-
yl)prop-20-ynyl]amino}-N0-p-tolyl benzamide 18. Light
yellow solid; mp 129±1318C; IR: nmax *KBr) 3165, 2228,
1
*neat) 3168, 2224, 1666, 1595 cm21; H NMR *60 MHz,
CCl4) d 2.33 *s, 3H, Ar±CH3), 2.95 *s, 3H, ±NCH3), 3.90
*s, 2H, ±NCH2), 6.72±7.62 *m, 10H, ArH), 8.03±8.26 *m,
1H, ArH), 11.70 *s, br, 1H, CONH). Anal. Calcd for
C22H20N2OS: C, 73.30; H, 5.59; N, 7.77. Found: C, 73.10;
H, 5.43; N, 7.63.
1
1664, 1597 cm21; H NMR *60 MHz, CCl4) d 2.26 *s, 3H,
Ar±CH3), 3.85 *s, 2H, ±NCH2), 3.86 *s, 3H, ±OCH3), 3.92
*s, 3H, ±OCH3), 4.33 *s, 2H, ±NCH2Ph), 6.92±7.66 *m,
13H, ArH), 8.20±8.50 *m, 1H, ArH), 11.65 *s, br, 1H,
±CONH). Anal. Calcd for C30H28N4O3: C, 73.15; H, 5.73;
N, 11.37. Found: C, 73.31; H, 5.89; N, 11.53.
4.2.7. 2-{N-Methyl-N-[30-ꢀ2,4-dimethoxypyrimidin-5-yl)-
prop-20-ynyl]amino}-N0-p-tolyl benzamide 12. Light
yellow sticky oil; IR: nmax *neat) 3163, 2243, 1668,
1
1596 cm21; H NMR *60 MHz, CCl4) d 2.33 *s, 3H, Ar±
4.3. General procedure for the synthesis of 19±31
CH3), 3.00 *s, 3H, ±NCH3), 3.96 *s, 6H, ±OCH3), 4.00 *s,
2H, ±NCH2), 6.95±7.66 *m, 8H, ArH), 8.06±8.33 *m, 1H,
ArH) 11.60 *s, br, 1H, CONH). Anal. Calcd for C24H24N4O3:
C, 69.21; H, 5.80; N, 13.45. Found: C, 68.92; H, 5.66; N,
13.25.
Amixture of the above disubstituted alkyne 6±18, CuI
*20 mol%), K2CO3 *2.5 equiv.) and Bu4NBr *1 equiv.) in
acetonitrile was re¯uxed for 16±24 h under argon
atmosphere. After removal of solvent under reduced pres-
sure and after usual work-up with chloroform±water, the
residue obtained after removal of chloroform was puri®ed
by column chromatography on neutral alumina using
chloroform±light petroleum ether *3:1) as eluent; the quina-
zolinones *19±31) were obtained as predominant products
*yield 60±67%).
4.2.8. 2-{N-Benzyl-N-[30-ꢀo-methylphenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 13. Colourless solid; mp
138±1398C; IR: nmax *KBr) 3161, 2225, 1665, 1600 cm21
;
1H NMR *60 MHz, CCl4) d 2.30 *s, 3H, Ar±CH3) 2.36 *s,
3H, Ar±CH3), 3.95 *s, 2H, ±NCH2), 4.40 *s, 2H,
±NCH2Ph), 6.82±7.66 *m, 16H, ArH), 8.26±8.40 *m, 1H,
ArH), 11.62 *s, br, 1H, CONH). Anal. Calcd for C31H28N2O:
C, 83.74; H, 6.34; N, 6.30. Found: C, 83.48; H, 6.17; N,
6.09.
4.3.1. 1-Methyl-ꢀE)-2-ꢀ2-phenylvinyl)-3-p-tolyl-1,2,3,4-
tetrahydroquinazolin-4-one 19. Colourless gum; IR: nmax
*neat) 1650, 1600 cm21; 1H NMR *300 MHz, CDCl3) d 2.26
*s, 3H, Ar±CH3), 2.85 *s, 3H, NCH3) 5.08 *d, Jˆ6.7 Hz, 1H,
N2CH), 6.29 *d, Jˆ15.9 Hz, 1H, vCHPh), 6.35 *dd,
J1ˆ6.7 Hz, J2ˆ15.9 Hz, 1H, HCvCPh), 6.58 *d,
Jˆ8.1 Hz, 1H, ArH), 6.83 *m, 1H, ArH), 7.09±7.22 *m,
9H, ArH), 7.30±7.36 *m, 1H, ArH), 7.98 *dd, J1ˆ1.5 Hz,
J2ˆ7.6 Hz, 1H, ArH); 13C NMR *75 MHz, CDCl3) d 21.53,
35.99, 81.84, 112.86, 117.70, 119.16, 123.19, 127.25,
128.90, 129.07, 129.77, 130.25, 130.42, 134.42, 134.67,
135.79, 137.41, 138.58, 147.38, 162.64; 13C NMR
4.2.9. 2-{N-Benzyl-N-[30-ꢀp-methylphenyl)prop-20-ynyl]-
amino}-N0-p-tolyl benzamide 14. Colourless solid; mp
1
1468C; IR: nmax *KBr) 3160, 1660, 1595 cm21; H NMR
*60 MHz, CCl4) d 2.30 *s, 3H, Ar±CH3), 2.36 *s, 3H, Ar±
CH3), 3.90 *s, 2H, ±NCH2), 4.40 *s, 2H, ±NCH2Ph), 6.85±
6.60 *m, 16H, ArH), 8.23±8.46 *m, 1H, ArH), 11.5 *s, br,
1H, ±CONH). Anal. Calcd for C31H28N2O: C, 83.74; H,
6.34; N, 6.30. Found: C, 83.57; H, 6.40; N, 6.58.

N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
6839
*75 MHz, CDCl3, DEPT 135) d 21.53, 35.99, 81.84, 112.87,
119.16, 123.19, 127.25, 127.29, 128.90, 129.07, 129.77,
130.25, 134.42, 134.67. Anal. Calcd for C24H22N2O: C,
81.32; H, 6.25; N, 7.90. Found: C, 81.28; H, 6.21; N,
7.83.
Anal. Calcd for C26H24N2O3: C, 75.70; H, 5.86; N, 6.79.
Found: C, 75.61; H, 5.74; N, 6.58.
4.3.6. 1-Methyl-ꢀE)-2-[2-ꢀ2-thienyl)vinyl]-3-p-tolyl-1,2,3,
4-tetrahydroquinazolin-4-one 24. Colourless solid; mp
1998C; IR: nmax *KBr) 1647, 1605 cm21
;
1H NMR
4.3.2. 1-Methyl-ꢀE)-2-[2-ꢀo-tolyl)vinyl]-3-p-tolyl-1,2,3,4-
tetrahydroquinazolin-4-one 20. Colourless gum; IR: nmax
*neat) 1651, 1606 cm21; 1H NMR *300 MHz, CDCl3) d 2.16
*s, 3H, Ar±CH3), 2.28 *s, 3H, Ar±CH3), 2.88 *s, 3H, NCH3),
5.12 *d, Jˆ7.8 Hz, 1H, N2CH), 6.15 *dd, J1ˆ7.8 Hz,
J2ˆ15.6 Hz, 1H, HCvCHAr), 6.58 *d, Jˆ15.6 Hz, 1H,
vCHAr), 6.59 *d, Jˆ8.4 Hz, 1H, ArH), 6.80±6.85 *m,
1H, ArH), 7.01±7.23 *m, 8H, ArH), 7.31±7.36 *m, 1H,
ArH), 7.95±7.98 *m, 1H, ArH); 13C NMR *75 MHz,
CDCl3) d 20.07, 21.51, 36.03, 81.78, 112.85, 117.84,
119.18, 124.69, 126.59, 127.30, 128.48, 128.70, 129.71,
130.21, 130.73, 132.80, 134.37, 135.20, 136.17, 137.40,
138.59, 147.41, 162.66; 13C NMR *75 MHz, CDCl3,
DEPT 135) d 19.78, 21.22, 35.74, 81.49, 112.56, 118.89,
124.40, 126.05, 126.30, 127.01, 128.41, 129.42, 129.93,
130.45, 132.51, 134.09. Anal. Calcd for C25H24N2O: C,
81.48; H, 6.56; N, 7.60. Found: C, 81.61; H, 6.64; N, 7.76.
*300 MHz, CDCl3) d 2.35 *s, 3H, Ar±CH3), 2.94 *s, 3H,
NCH3), 5.13 *d, Jˆ7.9 Hz, 1H, N2CH), 6.18 *dd,
J1ˆ7.9 Hz, J2ˆ15.6 Hz, 1H, HCvCHAr), 6.57 *d,
Jˆ15.6 Hz, 1H, vCHAr), 6.67 *d, Jˆ8.1 Hz, 1H, ArH),
6.89±6.93 *m, 3H, ArH), 7.15±7.28 *m, 5H, ArH), 7.40±
7.43 *m, 1H, ArH), 8.05 *dd, J1ˆ1.5 Hz, J2ˆ7.8 Hz, 1H,
ArH); 13C NMR *75 MHz, CDCl3) d 21.52, 36.06, 81.52,
112.91, 117.62, 119.19, 122.56, 125.78, 127.22, 127.56,
127.63, 127.90, 129.77, 130.26, 134.43, 137.42, 138.52,
140.71, 147.23, 162.63; 13C NMR *75 MHz, CDCl3,
DEPT 135) d 21.23, 35.77, 81.23, 112.62, 118.90, 122.27,
125.49, 126.93, 127.27, 127.35, 127.62, 129.48, 129.97,
134.14. Anal. Calcd for C22H20N2OS: C, 73.30; H, 5.59;
N, 7.77. Found: C, 73.16; H, 5.68; N, 7.97.
4.3.7. 1-Methyl-ꢀE)-2-[2-ꢀ2,4-dimethoxypyrimidin-5-yl)-
vinyl]-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-4-one 25.
Colourless solid; mp 708C; IR: nmax *KBr) 1651,
1
4.3.3. 1-Methyl-ꢀE)-2-[2-ꢀo-methoxyphenyl)vinyl]-3-p-
tolyl-1,2,3,4-tetrahydroquinazolin-4-one 21. Colourless
1595 cm21; H NMR *300 MHz, CDCl3) d 2.37 *s, 3H,
Ar±CH3), 2.94 *s, 3H, NCH3), 3.95 *s, 3H, OCH3), 3.96
*s, 3H, OCH3), 5.12 *d, Jˆ7.5 Hz, 1H, N2CH), 6.34 *d,
Jˆ15.9 Hz, 1H, vCHAr), 6.45 *dd, J1ˆ7.5 Hz,
J2ˆ15.9 Hz, 1H, HCvCHAr), 6.67 *d, Jˆ8.1 Hz, 1H,
ArH), 6.89±6.94 *m, 1H, ArH), 7.18±7.27 *m, 4H, ArH),
7.40±7.45 *m, 1H, ArH), 8.04 *dd, J1ˆ1.5 Hz, J2ˆ7.8 Hz,
1H, ArH), 8.13 *s, 1H, ArH). Anal. Calcd for C24H24N4O3:
C, 69.21; H, 5.80; N, 13.45. Found: C, 69.48; H, 5.83; N,
13.52.
;
gum; IR: nmax *neat) 1651, 1600 cm21 1H NMR
*300 MHz, CDCl3) d 2.23 *s, 3H, Ar±CH3), 2.85 *s, 3H,
NCH3), 3.68 *s, 3H, OCH3), 5.07 *d, Jˆ8.4 Hz, 1H,
N2CH), 6.33 *dd, J1ˆ8.4 Hz, J2ˆ14.7 Hz, 1H, HCvCHAr),
6.58 *d, Jˆ14.7 Hz, 1H, vCHAr), 6.69±6.85 *m, 4H, ArH),
7.09±7.36 *m, 7H, ArH), 7.98 *dd, J1ˆ1.5 Hz, J2ˆ7.5 Hz,
1H, ArH). Anal. Calcd for C25H24N2O2: C, 78.09; H, 6.29;
N, 7.28. Found: C, 77.90; H, 6.22; N, 7.12.
4.3.4. 1-Methyl-ꢀE)-2-[2-ꢀp-methoxyphenyl)vinyl]-3-p-
tolyl-1,2,3,4-tetrahydroquinazolin-4-one 22. Colourless
4.3.8. 1-Benzyl-ꢀE)-2-[2-ꢀo-tolyl)vinyl]-3-p-tolyl-1,2,3,4-
tetrahydroquinazolin-4-one 26. Colourless gum; IR: nmax
*neat) 1655, 1603 cm21; 1H NMR *300 MHz, CDCl3) d 2.15
*s, 3H, Ar±CH3), 2.28 *s, 3H, Ar±CH3), 4.26 *d, Jˆ15.1 Hz,
1H, NCHPh), 4.77 *d, Jˆ15.1 Hz, 1H, NCHPh), 5.20 *d,
Jˆ7.5 Hz, 1H, N2CH), 6.21 *dd, J1ˆ7.5 Hz, J2ˆ15.6 Hz,
1H, HCvCHAr), 6.52 *d, Jˆ15.6 Hz, 1H, vCHAr),
6.79±6.94 *m, 2H, ArH), 7.08±7.45 *m, 14H, ArH), 8.08
*dd, J1ˆ1.5 Hz, J2ˆ7.5 Hz, 1H, ArH). Anal. Calcd for
C31H28N2O:C, 83.74; H, 6.34; N, 6.30. Found: C, 83.80;
H, 6.51; N, 6.42.
gum; IR: nmax *neat) 1647, 1604 cm21
;
1H NMR
*300 MHz, CDCl3) 2.23 *s, 3H, Ar±CH3), 2.82 *s, 3H,
NCH3), 3.67 *s, 3H, OCH3), 5.04 *d, Jˆ8.1 Hz, 1H,
N2CH), 6.17 *dd, J1ˆ8.1 Hz, J2ˆ15.9 Hz, 1H, HCvCHAr),
6.30 *d, Jˆ15.9 Hz, 1H, vCHAr), 6.56 *d, Jˆ8.1 Hz, 1H,
ArH), 6.67±6.86 *m, 4H, ArH), 7.08±7.29 *m, 6H, ArH),
7.97 *dd, J1ˆ1.8 Hz, J2ˆ7.6 Hz, 1H, ArH). Anal. Calcd for
C25H24N2O2: C, 78.09; H, 6.29; N, 7.28. Found: C, 77.93; H,
6.25; N, 7.22.
4.3.5. 1-Methyl-ꢀE)-2-[2-ꢀo-methoxycarbonylphenyl)vinyl]-
3-p-tolyl-1,2,3,4-tetrahydroquinazolin-4-one 23. Colour-
less solid; mp 1698C; IR: nmax *KBr) 1713, 1666,
4.3.9. 1-Benzyl-ꢀE)-2-[2-ꢀp-tolyl)vinyl]-3-p-tolyl-1,2,3,4-
tetrahydroquinazolin-4-one 27. Colourless gum; IR: nmax
*neat) 1651, 1600 cm21; 1H NMR *300 MHz, CDCl3) d 2.30
*s, 3H, Ar±CH3), 2.31 *s, 3H, Ar±CH3), 4.23 *d, Jˆ15.4 Hz,
1H, NCHPh), 4.73 *d, Jˆ15.4 Hz, 1H, NCHPh), 5.15 *d,
Jˆ7.2 Hz, 1H, N2CH), 6.26 *d, Jˆ15.7 Hz, 1H, vCHAr),
6.35 *dd, J1ˆ7.2 Hz, J2ˆ15.7 Hz, 1H, HCvCHAr), 6.78 *d,
Jˆ8.1 Hz, 1H, ArH), 6.91±7.25 *m, 9H, ArH), 7.28±7.44
*m, 6H, ArH), 8.09 *dd, J1ˆ1.5 Hz, J2ˆ7.8 Hz, 1H, ArH).
Anal. Calcd for C31H28N2O: C, 83.74; H, 6.34; N, 6.30.
Found: C, 83.77; H, 6.41; N, 6.36.
1
1601 cm21; H NMR *300 MHz, CDCl3) d 2.27 *s, 3H,
Ar±CH3), 2.91 *s, 3H, NCH3), 3.75 *s, 3H, CO2Me), 5.15
*d, Jˆ8.4 Hz, 1H, N2CH), 6.19 *dd, J1ˆ8.4 Hz, J2ˆ15.3 Hz,
1H, HCvCHAr), 6.59 *d, Jˆ8.4 Hz, 1H, ArH), 6.82 *d,
Jˆ15.3 Hz, 1H, vCHAr), 7.11±7.36 *m, 9H, ArH), 7.81
*d, Jˆ8.1 Hz, 1H, ArH), 7.97 *dd, J1ˆ1.5 Hz, J2ˆ7.8 Hz,
1H, ArH); 13C NMR *75 MHz, CDCl3) d 21.51, 35.97,
52.49, 81.64, 112.81, 117.74, 119.06, 126.07, 126.09,
127.13, 128.19, 129.77, 130.19, 130.80, 131.03, 132.71,
134.18, 134.39, 137.27, 138.04, 138.67, 147.49, 162.61,
167.79; 13C NMR *75 MHz, CDCl3, DEPT 135) d 21.21,
35.65, 52.21, 81.33, 112.50, 118.75, 125.74, 126.82, 127.89,
128.09, 129.46, 129.90, 130.73, 132.41, 133.89, 134.10.
4.3.10.
tolyl-1,2,3,4-tetrahydroquinazolin-4-one 28. Colourless
gum; IR: nmax *neat) 1654, 1603 cm21 1H NMR
*300 MHz, CDCl3) d 2.29 *s, 3H, Ar±CH3), 4.24 *d,
1-Benzyl-ꢀE)-2-[2-ꢀm-chlorophenyl)vinyl]-3-p-
;

6840
N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
Jˆ15.3 Hz, 1H, NCHPh), 4.75 *d, Jˆ15.3 Hz, 1H, NCHPh),
5.18 *d, Jˆ7.3 Hz, 1H, N2CH), 6.23 *d, Jˆ15.9 Hz, 1H,
vCHAr), 6.37 *dd, J1ˆ7.3 Hz, J2ˆ15.9 Hz, 1H,
HCvCHAr), 6.81 *d, Jˆ8.4 Hz, 1H, ArH), 6.95±7.25 *m,
10H, ArH), 7.33±7.40 *m, 5H, ArH), 8.08 *dd, J1ˆ1.5 Hz,
J2ˆ7.8 Hz, 1H, ArH). Anal. Calcd for C30H25N2OCl: C,
77.48; H, 5.41; N, 6.02. Found: C, 77.34; H, 5.37; N,
5.86.
4.3.14. 1-Benzyl-ꢀZ)-3-[ꢀp-tolyl)methylidene]-4-p-tolyl-
1,2,3,4-tetrahydro-5H-benzodiazepin-5-one 32. Colour-
less gum; IR: nmax *neat) 1652, 1598 cm21 1H NMR
;
*300 MHz, CDCl3) d 2.25 *s, 3H, Ar±CH3), 2.27 *s, 3H,
Ar±CH3), 3.88 *s, 2H, ±CH2), 4.35 *s, 2H, ±CH2), 6.27 *s,
1H, vCH), 6.92±7.06 *m, 6H, ArH), 7.21±7.36 *m, 10H,
ArH), 7.66 *dd, J1ˆ1.8 Hz, J2ˆ7.6 Hz, 1H, ArH); 13C NMR
*75 MHz, CDCl3)
d
20.81, 21.19, 55.87, 63.96,
*3JCHˆ3.75 Hz), 118.64, 122.64, 122.78, 127.21, 127.94,
128.43, 128.76, 129.25, 129.33, 129.44, 130.55, 131.68,
131.71, 132.17, 135.03, 135.22, 136.51, 137.74, 138.54,
147.64, 169.23; 13C NMR *75 MHz, CDCl3, DEPT 135) d
21.02, 21.40, 56.07 *inverted), 64.17 *inverted), 118.85,
122.85, 122.99, 127.42, 128.15, 128.64, 128.97, 129.46,
129.54, 129.64, 131.91. Anal. Calcd for C31H28N2O: C,
83.74; H, 6.34; N, 6.30. Found: C, 83.90; H, 6.36; N, 6.33.
4.3.11. 1-Benzyl-ꢀE)-2-[2-ꢀo-methoxycarbonylphenyl)vi-
nyl]-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-4-one
29.
;
Colourless gum; IR: nmax *neat) 1717, 1655,1605 cm21
1H NMR *300 MHz, CDCl3) d 2.23 *s, 3H, Ar±CH3), 3.74
*s, 3H, ±CO2Me), 4.25 *d, Jˆ15.4 Hz, 1H, NCHPh), 4.68
*d, Jˆ15.4 Hz, 1H, NCHPh), 5.15 *d, Jˆ8.1 Hz, 1H,
N2CH), 6.18 *dd, J1ˆ8.1 Hz, J2ˆ15.1 Hz, 1H, HCvCHAr),
6.70 *d, Jˆ8.4 Hz, 1H, ArH), 6.83 *d, Jˆ15.1 Hz, 1H,
vCHAr), 7.04±7.12 *m, 5H, ArH), 7.15±7.42 *m, 9H,
ArH), 7.78 *d, Jˆ8.1 Hz, 1H, ArH), 8.01 *dd, J1ˆ1.5 Hz,
J2ˆ7.8 Hz, 1H, ArH). Anal. Calcd for C32H28N2O3: C,
78.66; H, 5.77; N, 5.73. Found: C, 78.45; H, 5.61; N,
5.63.
4.3.15. 1-Benzyl-ꢀZ)-3-[ꢀm-chlorophenyl)methylidene]-4-
p-tolyl-1,2,3,4-tetrahydro-5H-benzodiazepin-5-one 33.
Colourless gum; IR: nmax *neat) 1655, 1601 cm21 1H
;
NMR *300 MHz, CDCl3) d 2.25 *s, 3H, Ar±CH3), 3.94 *s,
2H, ±CH2), 4.37 *s, 2H, ±CH2), 6.23 *s, 1H, vCH), 6.99±
7.06 *m, 4H, ArH), 7.14±7.39 *m, 12H, ArH), 7.71 *m, 1H,
ArH). Anal. Calcd for C30H25N2OCl: C, 77.48; H, 5.41; N,
6.02. Found: C, 77.28; H, 5.31; N, 5.90.
4.3.12. 1-Benzyl-ꢀE)-2-[2-ꢀ2-thienyl)vinyl]-3-p-tolyl-1,2,
3,4-tetrahydroquinazolin-4-one 30. Colourless solid; mp
1
117±1188C; IR: nmax *KBr) 1657, 1601 cm21; H NMR
*300 MHz, CDCl3) d 2.31 *s, 3H, Ar±CH3), 4.25 *d,
Jˆ15.3 Hz, 1H, NCHPh), 4.75 *d, Jˆ15.3 Hz, 1H,
NCHPh), 5.15 *d, Jˆ7.5 Hz, 1H, N2CH), 6.16 *dd,
J1ˆ7.5 Hz, J2ˆ15.6 Hz, 1H, HCvCHAr), 6.44 *d,
Jˆ15.6 Hz, 1H, vCHAr), 6.8 *d, Jˆ8.4 Hz, 1H, ArH),
6.90±6.97 *m, 3H, ArH), 7.13±7.15 *m, 5H, ArH), 7.24±
7.42 *m, 6H, ArH), 8.09 *d, Jˆ7.8 Hz, 1H, ArH); 13C NMR
*75 MHz, CDCl3) d 21.49, 52.98, 78.39, 114.32, 118.71,
119.82, 122.97 125.70, 127.13, 127.20, 127.57, 127.88,
128.01, 128.31, 129.37, 129.91, 130.25, 134.29, 137.09,
137.33, 138.40, 140.84, 146.83, 162.69; 13C NMR*75 MHz,
CDCl3, DEPT 135) d 21.20, 52.70 *inverted), 78.11, 114.03,
119.53, 122.68, 125.41, 126.84, 126.91, 127.28, 127.60,
127.72, 128.02, 129.09, 129.63, 129.97, 134.00. Anal.
Calcd for C28H24N2OS: C, 77.03; H, 5.54; N, 6.41. Found:
C, 77.07; H, 5.50; N, 6.65.
4.3.16. 1-Benzyl-ꢀZ)-3-[ꢀ2-thienyl)methylidene]-4-p-tolyl-
1,2,3,4-tetrahydro-5H-benzodiazepin-5-one 34. Colourless
gum; IR: nmax *neat) 1658, 1649, 1596 cm21; 1H NMR
*300 MHz, CDCl3) d 2.28 *s, 3H, ArCH3), 3.86 *s, 2H,
±CH2), 4.33 *s, 2H, ±CH2), 6.62 *s, 1H, vCH), 6.89±6.99
*m, 4H, ArH), 7.06±7.32 *m, 10H, ArH), 7.53±7.62 *m, 2H,
ArH); 13C NMR *75 MHz, CDCl3) d 20.81, 55.74, 62.89
*3JCHˆ4.25 Hz), 118.63, 121.82, 122.69, 126.43, 126.67,
127.18, 127.85, 128.39, 128.42, 129.27, 129.37, 129.52,
131.68, 132.24, 133.38, 134.77, 135.62, 135.94, 137.60,
147.43, 169.11; 13C NMR *75 MHz, CDCl3, DEPT 135) d
21.02, 55.95 *inverted), 63.10 *inverted), 118.84, 122.02,
122.90, 126.64, 126.88, 127.39, 128.06, 128.63, 129.48,
129.58, 129.73, 131.90. Anal. Calcd for C28H24N2OS: C,
77.03; H, 5.54; N, 6.41. Found: C, 76.87; H, 5.44; N, 6.38.
4.3.17. Synthesis of 1-methyl-ꢀE)-2-[2-ꢀuracil-5-yl)vinyl]-
3-p-tolyl 1,2,3,4-tetrahydroquinazolin-4-one 35. To a
magnetically stirred solution of compound 25 *100 mg,
0.24 mmol) in dry acetonitrile *7 mL) under an argon
atmosphere were added anhydrous sodium iodide
*108 mg, 0.72 mmol) and trimethylchlorosilane *80 mg,
0.72 mmol). The resulting mixture was stirred at rt for
24 h. The solvent was removed under reduced pressure
and the residue was washed with a few drops of aqueous
sodium metabisul®te solution and then with cold water,
®ltered and dried to yield compound 35 as light yellow
powder solid *65 mg; 70%); mp.2008C; IR: nmax *KBr)
4.3.13. 1-Benzyl-ꢀE)-2-[2-ꢀ2,4-dimethoxypyrimidin-5-yl)-
vinyl]-3-p-tolyl-1,2,3,4-tetrahydroquinazolin-4-one 31.
Colourless solid; mp 708C; IR: nmax *KBr) 1659,
1
1595 cm21; H NMR *300 MHz, CDCl3) d 2.25 *s, 3H,
Ar±CH3), 3.95 *s, 3H, OCH3), 3.96 *s, 3H, OCH3) 4.27 *d,
Jˆ15.3 Hz, 1H, NCHPh), 4.75 *d, Jˆ15.3 Hz, 1H, NCHPh),
5.17 *d, Jˆ7.5 Hz, 1H, N2CH), 6.23 *d, Jˆ15.9 Hz, 1H,
vCHAr), 6.44 *dd, J1ˆ7.5 Hz, J2ˆ15.9 Hz, 1H,
HCvCHAr), 6.81 *d, Jˆ8.1 Hz, 1H, ArH), 6.91±6.96 *m,
1H, ArH), 7.14±7.17 *m, 4H, ArH), 7.22±7.44 *m, 6H,
ArH), 8.08±8.11 *m, 2H, ArH); 13C NMR *300 MHz,
CDCl3) d 21.48, 53.07, 54.53, 55.34, 78.99, 111.54,
114.28, 118.72, 119.76, 125.19, 125.36, 127.15, 128.05,
128.30, 129.34, 129.87, 130.23, 134.26, 137.10, 137.32,
138.44, 146.87, 157.29, 162.71, 164.89, 168.61; 13C NMR
*75 MHz, CDCl3, DEPT 135) d 21.20, 52.75 *inverted),
54.26, 55.06, 78.71, 113.97, 119.47, 124.91, 125.05,
126.87, 127.76, 128.01, 129.06, 129.58, 129.95, 133.98,
157.01. Anal. Calcd for C30H28N4O3: C, 73.15; H, 5.73; N,
11.37. Found: C, 73.05; H, 5.70; N, 11.33.
1
3030, 2925, 1715, 1680, 1595 cm21; H NMR *300 MHz,
CDCl31DMSO-d6) d 2.31 *s, 3H, ArCH3), 2.92 *s, 3H,
NCH3), 5.08 *d, Jˆ9.0 Hz, 1H, N2CH), 6.11 *d,
Jˆ15.0 Hz, 1H, vCH), 6.63 *dd, J1ˆ9.0 Hz, J2ˆ15.0 Hz,
1H, HCv), 6.85±6.90 *m, 1H, ArH), 7.13±7.16 *m, 3H,
ArH), 7.39±7.52 *m, 4H, ArH), 7.96 *d, Jˆ6.0 Hz, 1H,
vCH), 10.39 *s, 1H, ±NH), 10.87 *s, 1H, ±NH). Anal.
Calcd for C22H20N4O3: C, 68.02; H, 5.19; N, 14.42.
Found: C, 68.27; H, 5.06; N, 14.31.

N. G. Kundu, G. Chaudhuri / Tetrahedron 57 .2001) 6833±6842
6841
13. *a) Ra®, I.; Taylor, G. A.; Calvete, J. A.; Boddy, A. V.;
Balmano, K.; Boiby, N.; Lind, M.; Calvert, A. H.; Webber,
S.; Jackson, R. C.; Johnston, A.; Clendeninn, N.; Newell, D. R.
Clin. Cancer Res. 1995, 1, 1225. *b) Jackman, A. L.; Kimbell,
R.; Aherne, G. W.; Brunton, L.; Jansen, G.; Stephens, T. C.;
Smith, M. N.; Wardleworth, J. M.; Boyle, F. T. Clin. Cancer
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Similar reaction condition was used for the synthesis of 1-
benzyl-.E)-2-[2-.uracil-5-yl)vinyl]-3-p-tolyl-1,2,3,4-tetra-
hydroquinazolin-4-one 36 from 31.
Compound 36: *72%); light yellow powder solid;
mp.2008C; IR: nmax *KBr) 3032, 2920, 1713, 1674,
1584 cm21 1H NMR *300 MHz, CDCl31DMSO-d6) d
;
2.25 *s, 3H, ArCH3), 4.15 *d, Jˆ15.0 Hz, 1H, NCHPh),
4.64 *d, Jˆ15.0 Hz, 1H, NCHPh), 5.03 *d, Jˆ6.0 Hz, 1H,
N2CH), 5.90 *d, Jˆ15.5 Hz, 1H, vCH), 6.60 *dd,
J1ˆ6.0 Hz, J2ˆ15.5 Hz, 1H, HCv), 6.67 *d, Jˆ8.4 Hz,
1H, ArH), 6.82 *m, 1H, ArH), 7.02±7.07 *m, 4H, ArH),
7.14±7.46 *m, 7H, ArH), 7.94 *d, Jˆ6.0 Hz, 1H, ArH),
10.08 *s, 1H, ±NH), 10.77 *d, Jˆ3.0 Hz, 1H, ±NH). Anal.
Calcd for C28H24N4O3: C, 72.39; H, 5.20; N, 12.06. Found:
C, 72.22; H, 5.10; N, 11.97.
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