Novel approach for the synthesis of N-substituted-4-(2-methyl-4-oxo- 4hquinazolin- 3-YL)-butyramides

Article abstract of DOI:10.1080/00397911.2010.497594

A simple and convenient method for the synthesis of N-substituted-4-(2- methyl- 4-oxo-4H-quinazolin-3-yl)-butyramides has been reported. Several aromatic and aliphatic amide derivatives of 4-(2-methyl-4-oxo-4H-quinazolin-3- yl)-butyric acid were prepared

Full text of DOI:10.1080/00397911.2010.497594

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Novel Approach for the Synthesis of
N-Substituted-4-(2-methyl-4-oxo-4H-
quinazolin-3-yl)-butyramides
Mohammad Amir a & Israr Ali a
a Faculty of Pharmacy, Department of Pharmaceutical Chemistry ,
Hamdard University , New Delhi , India
Published online: 20 May 2011.
To cite this article: Mohammad Amir & Israr Ali (2011) Novel Approach for the Synthesis of N-
Substituted-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramides, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 41:14, 2086-2095,
DOI: 10.1080/00397911.2010.497594
To link to this article: http://dx.doi.org/10.1080/00397911.2010.497594
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Synthetic Communications1, 41: 2086–2095, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.497594
NOVEL APPROACH FOR THE SYNTHESIS OF
N-SUBSTITUTED-4-(2-METHYL-4-OXO-4H-
QUINAZOLIN-3-YL)-BUTYRAMIDES
Mohammad Amir and Israr Ali
Faculty of Pharmacy, Department of Pharmaceutical Chemistry,
Hamdard University, New Delhi, India
GRAPHICAL ABSTRACT
Abstract A simple and convenient method for the synthesis of N-substituted-4-(2-methyl-
4-oxo-4H-quinazolin-3-yl)-butyramides has been reported. Several aromatic and aliphatic
amide derivatives of 4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyric acid were prepared
in 60–81% yields by refluxing it with different phosphazo compounds in toluene for approxi-
mately 1 h.
Keywords c-Amino butyric acid; butyramides; phosphazo compounds; quinazolin-4-one
Quinazolin-4(3H)-one is one of the most versatile nuclei in medicinal chemistry, with
a
wide range of biological properties including antihypertensive,[1] anti-
inflammatory,[2] anticonvulsant,[3] antimicrobial,[4] antitumor,[5] antidiabetic,[6] and
antihistaminic[7] activities. A literature survey also revealed that the presence of a
substituted aromatic ring at position 3 and a methyl group at position 2 are neces-
sary requirements for central nervous system (CNS) depression and anticonvulsant
activities (methaqualone, Fig. 1).[8] It has been reported in literature that c-amino
butyric acid (GABA) is the principal inhibitory neurotransmitter in the mammalian
brain.[9] Further research has resulted in the discovery of GABA analogs such as
vigabatrin and gabapentin (Fig. 1) as useful anticonvulsant drugs.[10]
Because of the importance of a quinazolin-4(3H)-one moiety and GABA
analogs, our goal was to develop a convenient synthetic protocol for the design
and synthesis of amides of GABA-quinazolin-4(3H)-one analogs 5.
Received December 18, 2009.
Address correspondence to Mohammad Amir, Faculty of Pharmacy, Department of
Pharmaceutical Chemistry, Hamdard University, Hamdard Nagar, New Delhi 110062, India. E-mail:
mamir_s2003@yahoo.co.in
2086

QUINAZOLIN-4-ONE BUTYRAMIDES
2087
Figure 1. Anticonvulsant drugs.
Although there are a number of synthetic methods available for the preparation
of quinazolin-4(3H)-one derivatives,[11] synthesis of its amide derivatives having an
alkanoic acid side chain has not been reported in literature. Therefore, our objective
in the present work is to develop a simple and efficient method for the synthesis of
amide derivatives of quinazolin-4(3H)-one having a butyric acid side chain 5.
Whereas various methods have been described in literature for amide coupling
reactions, our initial approach was to obtain amide derivatives by converting acid 1
into an acid chloride with SOCl2 and then treatment with an amine in the presence of
triethylamine and dry acetone (i).[12] However, NMR and mass spectral analysis of
the resulting product showed the absence of an aliphatic side chain and molecular
ion peak, respectively, thus confirming that formation of the amide did not take
place. Instead, the spectra confirmed the formation of compound 2 (Scheme 1).
Amide formation is also reported between a carboxylic acid and a free amino
group on treatment with N,N-dicyclohexylecarbodiimide (DCC) at room tempera-
ture (ii),[13] so we tried this method for preparation of amide 5 of 4-(2-methyl-
4-oxo-4H-quinazolin-3-yl)-butyric acid 1. The reaction was carried out at room
temperature, 0 ꢀC, ꢁ10 ꢀC, and even refluxing temperature for 6 to 10 h in
dichloromethane (DCM). The products thus obtained in the reaction conditions
were purified by column chromatography using hexane–ethyl acetate mobile phase,
and they were found to be the same. When the pure compounds thus obtained were
analyzed by NMR and mass spectroscopy, we were surprised to observe that
expected peaks of an aliphatic side chain as well as amide linkage and molecular
ion peak were missing in the NMR and mass spectra respectively, and the product
was identified as compound 2 (Scheme 1).
Amide formation is also reported between a carboxylic acid and a free amino
group in the presence of another advance coupling agent, 1-[3-(dimethylamino)pro-
pyl]-3-ethyl-carbodiimide hydrochloric acid (EDC) and 1-hydroxybenzotriazole
(HOBt) in equivalent ratio at 0 ꢀC.[14] Therefore, this coupling reagent (EDC=HOBt)
was employed for the synthesis of the desired amide (1) in the presence of 20%
Scheme 1. Reagents and conditions.

2088
M. AMIR AND I. ALI
Scheme 2. Plausible mechanism.
dimethylformamide (DMF)–CH2Cl2 at 0 ꢀC (iii), but NMR and mass spectral data
of the resulting product were not in agreement with desired product 5, and the
product was the same as compound 2 (Scheme 1).
On the basis of all these results, it was observed that instead of amide formation,
the substituted amines are replacing the N-(CH2)3COOH group from the third pos-
ition of the quinazolin-4(3H)-one ring,[15] and formation of 3-alkyl=aryl-2-methyl-
3H-quinazolin-4-one 2 is taking place (Scheme 2). Thus, we concluded that even in
the presence of these advance coupling reagents, the free amino group is not able to
form the amide linkage of 4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyric acid (1).
Thus, with a free amino (-NH2) group, the formation of amide 5 was not poss-
ible. Therefore, we searched for an alternative method in which the amino (-NH2)
group must not be in the free form, and we found that interaction of carboxylic acids
and amines in the presence of phosphorous trichloride to form N-substituted amides
is reported in literature.[16] In the initial reaction, amines react with phosphorous
trichloride to form the phosphazo compound 3. On heating, the phosphazo com-
pound 3 reacts with carboxylic acid to give an amide (Scheme 3).
Thus, we used the application of phosphazo compounds in the preparation of
amide analogs of 4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyric acid 1. The forma-
tion of amide derivatives 5a–m takes place when compound 1 is refluxed with
phosphazo compounds 3a–m in toluene. We also used different solvents such as
Scheme 3. Formation of phosphazo compounds and their amide derivatives.

QUINAZOLIN-4-ONE BUTYRAMIDES
2089
Scheme 4. Formation of amide analogs using phosphazo compounds.
dichloromethane, chloroform, and xylene in different reaction conditions to opti-
mize the reaction time and yield, but the best result was obtained (60–81% yield)
when toluene was used as a solvent at refluxing temperature for 1 h (Scheme 4).
1
The amides thus obtained were characterized by H NMR, 13C NMR, and mass
1
spectral data. The H NMR spectral data of compounds 5a–m showed a triplet of
a CH2 protons from d 2.12 to 2.48 ppm. The b CH2 protons were observed as a mul-
tiplet from d 1.50 to 2.16 ppm. The c CH2 protons appeared as a triplet from d 3.18
to 4.22 ppm. Furthermore, the NH proton of amide linkage was observed as a broad
singlet from d 5.26 to 10.00 ppm. 13C NMR spectra of the compounds 5a–m also
showed the signals of a, b, and c carbons in the spectra. Furthermore, the carbonyl
carbon of amide linkage appeared downfield from d 170.0 to 171.6, confirming
formation of the amide derivatives.
In conclusion, we have reported an efficient and convenient one-step synthesis
of biologically important N-substituted-4-(2-methyl-4-oxo-4H-quinazolin-3-
yl)-butyramides under mild reaction conditions. The reaction is applicable to a wide
range of aliphatic and aromatic amines. The purposed reaction mechanism for this
process involves utilization of 2 mol of acid for every 1 mol of phosphazo compound
(Scheme 5). Work is under way in our laboratory to further explore the scope of this
reaction.
Scheme 5. Plausible mechanism for the amide formation.

2090
M. AMIR AND I. ALI
EXPERIMENTAL
Melting points were determined in one-end open capillary tubes on a Buchi 530
melting-point apparatus and are uncorrected. Proton nuclear magnetic resonance
(1H NMR) spectra were measured on Bruker Avance-400 instrument (400 MHz).
Carbon nuclear magnetic resonance (13C NMR) spectra were measured on Bruker
Avance-400 instrument (100 MHz) with complete proton decoupling. Chemical
shifts are reported in parts per million (ppm) downfield from tetramethylsilane
(TMS). Elemental analyses (C, H, and N) were undertaken with a CHNS Elementar
(Analysen Systime, GmbH, Germany) Vario EL III. The reactions were monitored
by silica gel–GF coated aluminum plates and visualized by iodine vapors and ultra-
violet light as visualizing agents. Mass (MS) spectral data were recorded in
electron-impact (EI) mode. Removal of solvents was carried out at reduced pressure
using a rotary evaporator. Solid products were purified by recrystallization.
Synthesis of 4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-butyric Acid 1
Freshly prepared 2-methyl-benzo[d][1,3]oxazin-4-one[17] 4 (3.75 g, 23.29 mmol,
1.0 equiv) was dissolved in absolute ethanol in a dry and clean round-bottomed flask
with condenser and guard tube. 4-Amino-butyric acid (2.02 g, 23.29 mmol, 1.0 equiv)
was added to it, and the resulting solution was refluxed for about 2 h. The progress of
reaction was monitored by aluminum-coated Merck thin-layer chromatography
(TLC) plates using 60% ethyl acetate–hexane solvent system. The solvent was
removed by rotary evaporator up to half of its volume, poured into ice-cooled water,
and kept aside overnight. The crystals thus obtained were filtered, dried, and recrys-
1
tallized by methanol (yield 70%). Rf value 0.30. H NMR (400 MHz, DMSO-d6): d
9.50 (br s, 1H, COOH), 8.45 (d, 1H, J ¼ 8.0 Hz, 5th ArH), 7.97 (d, 1H, J ¼ 7.6 Hz,
8th ArH), 7.30 (t, 1H, J ¼ 8.4 Hz, 6th ArH), 6.96 (t, 1H, J ¼ 7.6 Hz, 7th ArH),
2.84 (t, 2H, J ¼ 7.2 Hz, NCH2), 2.36 (t, 2H, J ¼ 7.2 Hz, COCH2), 1.79 (m, 2H,
CH2); MS (EI) m=z (%): 247.5 (100) [M þ 1]. Anal. calcd. for C13H14N2O3: C,
63.40; H, 5.73; N, 11.38. Found: C, 63.25; H, 5.78; N, 11.40.
Typical Procedure for Preparation of Phosphazo Compounds 3a–m
A solution of PCl3 (1 equiv) in toluene (10 mL) was added to a solution of pri-
mary amines (5 equiv) in toluene (20–30 mL) slowly at low temperature (0–5 ꢀC).
Separation of solid was observed on addition of PCl3 solution due to formation of
hydrochloric salt of amines. The reaction mixture was further stirred at room tem-
perature for approximately 1 h for completion of the reaction. The hydrochloric salts
of amines were filtered under dry condition, and the filtrate containing phosphazo
compounds (3a–m) was used in the next step.
Typical Procedure for Preparation of Amides 5a–m
4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-butyric acid 1 (2 equiv) was added to
the filtrate containing phosphazo compounds 3a–m, and the solution was refluxed
for approximately 1 h. Separation of orange gummy precipitate of metaphosphorous

QUINAZOLIN-4-ONE BUTYRAMIDES
2091
acid (HPO2) at the bottom of the flask indicated the formation of product. The
progress of the reaction was monitored by aluminum-coated Merck TLC plates
using 100% ethyl acetate solvent system, Rf value 0.4–0.6. The hot toluene solution
was decanted slowly in a 100-mL conical flask. The flask was rinsed with hot toluene
(10 mL). The solution was again decanted in the previous solution of toluene and
was kept at room temperature overnight. The amides, which separated out as a white
crystalline solid, were filtered and dried in air. The compounds 5a–m thus obtained
were further purified by crystallizing with ethyl acetate. Yield 64–81%.
Characterization Data for Products
4-(2-Methyl-oxo-4H-quinazolin-3-yl)-N-propyl-butyramide (5a). White
1
solid, yield 81%. Rf value 0.5, mp: 108–110 ꢀC. H NMR (400 MHz, CDCl3): d
8.20 (d, 1H, J ¼ 8.0 Hz, 5th ArH), 7.69 (t, 1H, J ¼ 8.0 Hz, 6th ArH), 7.59 (d, 1H,
J ¼ 8.0 Hz, 8th ArH), 7.40 (t, 1H, J ¼ 7.6 Hz, 7th ArH), 6.12 (bs, 1H, CONH),
4.13 (t, 2H, J ¼ 7.6 Hz, ArNCH2), 3.16 (q, 2H, J ¼ 6.8 Hz, NCH2), 2.68 (s, 3H,
CH3), 2.30 (t, 2H, J ¼ 6.4 Hz, CH2CO), 2.06 (m, 2H, ArNCH2CH2), 1.50 (m, 2H,
CH2), 0.89 (t, 3H, J ¼ 5.2 Hz, CH3); 13C NMR (100 MHz, CDCl3): d 171.6, 162.4,
154.3, 149.6, 134.6, 126.7, 126.6, 126.4, 120.3, 43.7, 41.3, 33.1, 25.6, 23.1, 22.8,
11.4; MS (EI) m=z (%): 288.3 (100) [M þ 1]. Anal. calcd. for C16H21N3O2: C,
66.88; H, 7.37; N, 14.62. Found: C, 66.66; H, 7.33; N, 14.54%.
4-(2-Methyl-oxo-4H-quinazolin-3-yl)-N-iso-propyl-butyramide (5b). White
1
solid, yield 68%. Rf value 0.5, mp: 148–150 ꢀC. H NMR (400 MHz, CDCl3): d 8.16
(d, 1H, J ¼ 8.0 Hz, 5th ArH), 7.65 (t, 1H, J ¼ 8.4 Hz, 6th ArH), 7.55 (d, 1H,
J ¼ 8.0 Hz, 8th ArH), 7.36 (t, 1H, J ¼ 7.6 Hz, 7th ArH), 6.07 (bs, 1H, CONH),
4.09 (t, 2H, J ¼ 7.6 Hz, ArNCH2), 4.03 (m, 1H, CH), 2.65 (s, 3H, CH3), 2.25 (t,
2H, J ¼ 6.8 Hz, CH2CO), 2.00 (m, 2H, CH2), 1.10 (d, 6H, J ¼ 6.8 Hz, (CH3)2); 13C
NMR (100 MHz, CDCl3): d 170.7, 162.3, 154.3, 147.2, 134.2, 126.64, 126.60,
126.3, 120.2, 43.8, 41.4, 33.1, 24.5, 23.0, 22.6. Anal. calcd. for C16H21N3O2: C,
66.88; H, 7.37; N, 14.62. Found: C, 66.65; H, 7.34; N, 14.53%.
N-Butyl-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide (5c). White
1
solid, yield 70%. Rf value 0.45, mp: 130–132 ꢀC. H NMR (400 MHz, CDCl3): d
8.16 (d, 1H, J ¼ 7.6 Hz, 5th ArH), 7.66 (t, 1H, J ¼ 8.0 Hz, 6th ArH), 7.56 (d, 1H,
J ¼ 8.0 Hz, 8th ArH), 7.37 (t, 1H, J ¼ 7.6 Hz, 7th ArH), 6.17 (bs, 1H, CONH),
4.10 (t, 2H, J ¼ 6.8 Hz, ArNCH2), 3.18 (q, 2H, J ¼ 6.4 Hz, NCH2), 2.65 (s, 3H,
CH3), 2.28 (t, 2H, J ¼ 6.4 Hz, CH2CO), 2.03 (m, 2H, ArNCH2CH2), 1.44 (m, 2H,
NCH2CH2), 1.33 (m, 2H, NCH2CH2CH2), 0.85 (t, 3H, J ¼ 7.2 Hz, CH3); 13C
NMR (100 MHz, CDCl3): d 171.6, 163.4, 154.3, 147.3, 134.3, 126.69, 126.60,
126.3, 120.2, 49.3 43.8, 40.5, 39.3, 33.0, 24.3, 23.1, 20.0. Anal. calcd. for
C17H23N3O2: C, 67.75; H, 7.69; N, 13.94. Found: C, 67.74; H, 7.66; N, 13.95%.
N-t-Butyl-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide (5d). White
1
solid, yield 65%. Rf value 0.40, mp: 96–98 ꢀC. H NMR (400 MHz, CDCl3): d 8.19
(d, 1H, J ¼ 8.0 Hz, 5th ArH), 7.68 (t, 1H, J ¼ 6.8 Hz, 6th ArH), 7.58 (d, 1H,
J ¼ 8.0 Hz, 8th ArH), 7.39 (t, 1H, J ¼ 7.6 Hz, 7th ArH), 5.73 (bs, 1H, CONH),
4.11 (t, 2H, J ¼ 7.2 Hz, NCH2), 2.66 (s, 3H, CH3), 2.22 (t, 2H, J ¼ 6.8 Hz, CH2CO),

2092
M. AMIR AND I. ALI
2.03 (m, 2H, CH2), 1.29 (m, 9H, (CH3)3); 13C NMR (100 MHz, CDCl3): d 171.0,
162.3, 154.4, 148.6, 134.3, 126.6, 126.3, 121.0, 54.9, 51.2, 34.0, 28.7, 24.3, 23.0; MS
(EI) m=z (%): 302.3 (100) [M þ 1]. Anal. calcd. for C17H23N3O2: C, 67.75; H, 7.69;
N, 13.94. Found: C, 67.73; H, 7.64; N, 13.96%.
N-Cyclohexyl-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide (5e). White
1
solid, yield 68%. Rf value 0.45, mp: 177–179 ꢀC. H NMR (400 MHz, DMSO-d6):
d 8.06 (d, 1H, J ¼ 7.6 Hz, 5th ArH), 7.75–7.70 (q, 2H, 6th ArH & CONH), 7.54
(d, 1H, J ¼ 8.4 Hz, 8th ArH), 7.43 (t, 1H, J ¼ 7.2 Hz, 7th ArH), 3.98 (t, 2H,
J ¼ 6.8 Hz, NCH2), 3.22 (m, 1H, CH of cyc-hex), 2.57 (s, 3H, CH3), 2.12 (t, 2H,
J ¼ 6.4 Hz, CH2CO), 1.84–0.81 (m, 12H, CH2 & cyc-hex.); 13C NMR (100 MHz,
DMSO-d6): d 170.6, 161.5, 155.4, 147.5, 134.6, 126.9, 126.6, 120.4, 47.8, 43.9, 32.9,
25.7, 25.0, 24.4, 23.1; MS (EI) m=z (%): 328.7 (100) [M þ 1]. Anal. calcd. for
C19H25N3O2: C, 69.70; H, 7.70; N, 12.83. Found: C, 69.75, H, 7.67; N, 12.86%.
4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-N-phenyl-butyramide (5f). White
1
solid, yield 64%. Rf value 0.6, mp: 139–141 ꢀC. H NMR (400MHz, DMSO-d6): d
10.0 (s, 1H, CONH), 8.07 (d, 1H, J ¼ 8.0 Hz, 5th ArH), 7.97–6.74 (m, 8H, ArH),
4.06 (t, 2H, J ¼ 7.6 Hz, NCH2), 2.61 (s, 3H, CH3), 2.42 (t, 2H, J ¼ 6.4 Hz, CH2CO),
1.94 (m, 2H, CH2); 13C NMR (100MHz, CDCl3): d 170.8, 161.6, 155.4, 147.5, 139.6,
134.6, 129.1, 126.9, 126.6, 123.4, 120.9, 119.5, 117.8 43.9, 33.8, 24.1, 23.1. Anal. calcd.
for C19H19N3O2: C, 71.01; H, 5.96; N, 13.08. Found: C, 71.15; H, 5.94; N, 13.10%.
N-(4-Chlorophenyl)-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide
1
(5g). White solid, yield 75%. Rf value 0.5, mp: 207–209 ꢀC. H NMR (400 MHz,
CDCl3): d 8.22 (d, 1H, J ¼ 8.0 Hz, 5th ArH), 8.11 (bs, 1H, CONH), 7.71 (t, 1H,
J ¼ 8.0 Hz, 6th ArH), 7.62 (d, 1H, J ¼ 8.4 Hz, 8th ArH), 7.41 (m, 3H, ArH), 7.10
(d, 2H, J ¼ 8.4 Hz, ArH), 4.01 (t, 2H, J ¼ 7.2 Hz, NCH2), 2.71 (s, 3H, CH3), 2.45
(t, 2H, J ¼ 6.0 Hz, CH2CO), 2.12 (m, 2H, CH2); MS (EI) m=z (%): 356.5 (100)
[M þ 1], 358.5 (32.5) [M þ 2]. Anal. calcd. for C19H18ClN3O2: C, 64.13; H, 5.10;
N, 11.81. Found: C, 64.21; H, 5.13; N, 11.84%.
N-(4-Fluorophenyl)-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide
1
(5h). White solid, yield 80%. Rf value 0.6, mp: 167–169 ꢀC. H NMR (400 MHz,
CDCl3 þ DMSO-d6): d 9.99 (bs, 1H, CONH), 8.07 (d, 1H, J ¼ 7.6 Hz, 5th ArH),
7.75–6.63 (m, 7H, ArH), 4.08 (t, 2H, J ¼ 6.8 Hz, NCH2), 2.62 (s, 3H, CH3), 2.42
(t, 2H, J ¼ 6.8 Hz, CH2CO), 1.96 (m, 2H, CH2); 13C NMR (100 MHz, DMSO-d6):
d 170.7, 161.6, 155.4, 147.5, 134.6, 126.8, 126.6, 126.5, 121.8, 121.2, 120.4, 115.7,
115.4, 43.8, 33.7, 24.1, 23.0; MS (CI) m=z (%): 340.5 (100) [M þ 1]. Anal. calcd.
for C19H18FN3O2: C, 67.24; H, 5.35; N, 12.38. Found: C, 67.28; H, 5.37; N, 12.35%.
N-(3-Chloro-4-fluorophenyl)-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-
1
butyramide (5i). White solid, yield 64%. Rf value 0.5, mp: 202–204 ꢀC. H NMR
(400 MHz, DMSO-d6): d 9.90 (bs, 1H, CONH), 8.08–6.2 (m, 7H, ArH), 4.10 (t, 2H,
J ¼ 7.2 Hz, NCH2), 2.62 (s, 3H, CH3), 2.40 (t, 2H, J ¼ 6.8 Hz, CH2CO), 2.00 (m, 2H,
CH2); 13C NMR (100 MHz, DMSO-d6): d 170.7, 161.8, 154.6, 147.4, 134.1, 126.7,
126.5, 126.2, 121.2, 120.3, 119.9, 119.8, 116.7, 116.5, 116.3, 43.7, 33.6, 24.0, 23.1.
Anal. calcd. for C19H17ClFN3O2: C, 61.05; H, 4.58; N, 11.24. Found: C, 61.11; H,
4.60; N, 11.22%.

QUINAZOLIN-4-ONE BUTYRAMIDES
2093
4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-N-o-tolyl-butyramide (5j). White
1
solid, yield 66%. Rf value 0.5, mp: 180–182 ꢀC. H NMR (400 MHz, CDCl3): d
8.22 (d, 1H, J ¼ 7.2 Hz, 5th ArH), 7.73–6.90 (m, 7H, ArH), 5.26 (bs, 1H, CONH),
4.23 (t, 2H, NCH2), 2.71 (s, 3H, CH3), 2.54 (t, 2H, CH2CO), 2.29 (s, 3H, CH3),
2.16 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): d 170.3, 162.5, 154.4, 147.1,
137.9, 134.4, 130.8, 130.5, 127.1, 126.7, 126.5, 125.4, 123.6, 122.8, 118.8, 43.7,
33.8, 24.6, 23.0, 17.6; MS (EI) m=z (%): 336.2 (100) [M þ 1]. Anal. calcd. for
C20H21N3O2: C, 71.62; H, 6.31; N, 12.53. Found: C, 71.65; H, 6.33; N, 12.56%.
4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-N-p-tolyl-butyramide (5k). White
solid, yield 72%. Rf value 0.55, mp: 161–163 ꢀC. 1H NMR (400 MHz, CDCl3): d 8.25
(d, 1H, J ¼ 8.0 Hz, 5th ArH), 8.11 (bs, 1H, CONH), 7.72 (t, 1H, J ¼ 8.0 Hz, 6th
ArH), 7.61 (d, 1H, J ¼ 8.4 Hz, 8th ArH), 7.44 (m, 3H, ArH), 7.11 (d, 2H, J ¼ 8.4 Hz,
ArH), 4.22 (t, 2H, J ¼ 7.2 Hz, NCH2), 2.71 (s, 3H, CH3), 2.48 (t, 2H, J ¼ 6.0 Hz,
CH2CO), 2.30 (s, 3H, CH3), 2.16 (m, 2H, CH2); 13C NMR (100 MHz, CDCl3): d
170.1, 162.7, 158.6, 154.2, 135.4, 134.4, 133.8, 129.4, 126.74, 126.71, 126.5, 120.2,
120.0, 43.7, 35.9, 24.4, 23.1, 20.6. Anal. calcd. for C20H21N3O2: C, 71.62; H, 6.31;
N, 12.53. Found: C, 71.67; H, 6.35; N, 12.55%.
N-(4-Methoxyphenyl)-4-(2-methyl-4-oxo-4H-quinazolin-3-yl)-butyramide
1
(5l). White solid, yield 79%. Rf value 0.5, mp: 160–162 ꢀC. H NMR (400 MHz,
CDCl3): d 8.28 (bs, 1H, CONH), 8.23 (d, 1H, J ¼ 7.6 Hz, 5th ArH), 7.71 (t, 1H,
J ¼ 7.6 Hz, 6th ArH), 7.61 (d, 1H, J ¼ 8.0 Hz, 8th ArH), 7.44 (d, 2H, J ¼ 8.8 Hz,
ArH), 7.42 (d, 1H, J ¼ 7.6 Hz, 7th ArH), 6.84 (d, 2H, ArH), 4.21 (t, 2H, J ¼ 7.2 Hz,
NCH2), 3.77 (s, 3H, OCH3), 2.70 (s, 3H, CH3), 2.48 (t, 2H, J ¼ 6.0 Hz, CH2CO), 2.14
(m, 2H, CH2); 13C NMR (100 MHz, CDCl3): d 170.0, 162.7, 156.3, 154.2, 147.3,
134.4, 131.1, 126.7, 126.6, 126.5, 121.7, 120.2, 114.1, 55.4, 43.7, 33.9, 24.4, 23.1;
MS (CI) m=z (%): 352.3 (100) [M þ 1]. Anal. calcd. for C20H21N3O3: C, 68.36; H,
6.02; N, 11.96. Found: C, 68.40; H, 6.10; N, 11.95%.
4-(2-Methyl-4-oxo-4H-quinazolin-3-yl)-N-naphthalen-1-yl-butyramide
1
(5m). White solid, yield 60%. Rf value 0.55, mp: 219–221 ꢀC. H NMR (400 MHz,
DMSO-d6): d 9.89 (bs, 1H, CONH), 8.10–7.3 (m, 11H, ArH), 4.02 (t, 2H, J ¼ 7.2 Hz,
NCH2), 2.62 (s, 3H, CH3), 2.25 (t, 2H, J ¼ 6.4 Hz, CH2CO), 2.04 (m, 2H, CH2); MS
(EI) m=z (%): 373.6 (100) [M þ 1]. Anal. calcd. for C23H21N3O2: C, 74.37; H, 5.70; N,
11.31. Found: C, 74.21; H, 5.76; N, 11.33%.
ACKNOWLEDGMENT
We are grateful to the University Grants Commission (UGC), New Delhi,
India, for financial support.
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