A solvent-free protocol for one pot conversion of Baylis Hillman acetates to pyridopyrimidinones

Article abstract of DOI:10.1002/jhet.560

A facile one pot transformation of Baylis Hillman acetates to pyrido[1,2-a]pyrimidin-2-ones by reaction with 2-amino pyridine in a total solvent-free protocol is illustrated. The 3-substituted-2H-pyrido[1,2-a] pyrimidin-2-ones are obtained in pure form without involving any purification technique or solvent.

Full text of DOI:10.1002/jhet.560

586
A Solvent-Free Protocol for One Pot Conversion of Baylis
Hillman Acetates to Pyridopyrimidinones
Vol 48
R. Sreevani, A. Manjula, and B. Vittal Rao*
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500607, India
*E-mail: vittalrao@iict.res.in, raobommena@gmail.com
Received February 5, 2010
DOI 10.1002/jhet.560
Published online 4 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
A facile one pot transformation of Baylis Hillman acetates to pyrido[1,2-a]pyrimidin-2-ones by reac-
tion with 2-amino pyridine in a total solvent-free protocol is illustrated. The 3-substituted-2H-pyr-
ido[1,2-a]pyrimidin-2-ones are obtained in pure form without involving any purification technique or
solvent.
J. Heterocyclic Chem., 48, 586 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
Pyrimidines are integral constituents of cellular mo-
lecular framework like DNA, RNA [1], etc. Heterofused
pyrimidines have been found to exhibit antiviral [2],
antibacterial [3], anti-AIDS [4], antiplatelet [5], antith-
rombotic[6], antinociceptive [7] activities, etc. Their
applications were especially attractive due to their inhi-
bition of multidrug resistance [8]. Among the fused pyr-
imidines, pyrido[1,2-a]pyrimidinone motif is an essential
part of marketed pharmaceuticals like the antiasthamatic
pemirolast (A) [9], an antiulcerative drug (B) [10], the
tranquillizer pirenperone (C) [11], and the antiallergic
barmastine (D) [12] (Figure 1). The diverse biological
activities exhibited by these structural moieties justify
our interest in further exploration of the pyrido[1,2-
a]pyrimidin-2-ones for potential applications in agro-
chemical and pharmaceutical area.
At the outset, we attempted the one pot reaction of
methyl 2-(acetoxy(phenyl)methyl)acrylate (1a) with 2-
aminopyridine (2) under the conditions described by
Basavaiah and Satyanarayana [18]. The reaction pro-
ceeds in (1:1) MeOH, H2O solvent mixture to produce
3-benzyl-2H-pyrido [1,2-a]pyrimidin-2-one (3a) in 6 h
and 75% yield. As we planned to prepare a library of
compounds in an efficient and quick manner for an
ongoing project work, we have relooked at this well-
known reaction, seeking improvisation. Initially, a sol-
vent-free condensation has been attempted (Scheme 1).
To our surprise, the reaction proceeded within minutes,
and solid product was precipitated out. Mere filtration of
the reaction mixture by trituration with water gave prod-
uct 3a (entry 1, Table 1) pure enough for all purposes
including high-resolution mass spectrometry. The spec-
tral data and melting points of 3a were comparable with
those of reported in literature [18] further proving that
no purification of the product was essential.
Pyrido[1,2-a]pyrimidines have been synthesized by
different methods depending on the side chains/ring sub-
stitutions required. Condensation of 2-aminopyridine
with alkyl acrylates [13], methyl propiolate [14], di-
methyl allene-1,3-dicarboxylate [15], diethyl N,N-dime-
thylaminomethylene malonate [16], a-acetyl-c-butyro-
lactone [17], etc., have been attempted. Transformation
of Baylis Hillman acetates by condensation with 2-ami-
nopyridine to 3-substituted-2H-pyrido[1,2-a]pyrimidin-2-
ones has also been reported [18]. Versatility of this reac-
tion found to be more suitable for generating diversely
substituted 2H-pyrido[1,2-a]pyrimidin-2-ones library of
compounds for exploring their biological potential.
Inspired by this result, we then went on to test the
scope of this total solvent-free conversion by varying
both the Baylis Hillman acetates and substitutions on 2-
aminopyridine. The representative set of acetates and 5-
substituted-2-aminopyridines exploited are listed in
Table 1. All transformations were facile and occurred at
room temperature in good yields. In all cases, the pure
products were obtained by simple filtration. The trans-
formations with simple 2-aminopyridine were rapid
and occurred within few minutes. Reaction with
C
V
2011 HeteroCorporation

May 2011
A Solvent-Free Protocol for One Pot Conversion of Baylis Hillman Acetates to
Pyridopyrimidinones
587
lengthy workup or purification techniques, thus enhanc-
ing its synthetic utility. The biological profile of the syn-
thesized substituted 2H-pyrido[1,2-a]pyrimidin-2-ones is
being investigated and will be published elsewhere.
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. NMR spectra were obtained on JCAMP DX-50
instrument (300 MHz for 1H and 75 MHz for 13C), and
CDCl3 and DMSO-d6 used as solvents; J values are in Hz.
Chemical shifts are reported in d (ppm) down field from in-
ternal standared TMS. Electronic ionization MS spectra were
recorded on thermofunigan ESI ion trap mass spectrometer.
HRMS data were recorded on QSTAR XL Hybrid MS/MS
system under ESI condition. IR spectra were recorded on a
Thermo Nicolet NEXUS 670 spectrometer in KBr with
Figure 1. Marketed pharmaceuticals with pyrido[1,2-a]pyrimidinone
motif.
5-substituted-2-aminopyridines on the other hand was
little slow, taking few hours to complete. The yield was
better with halo substitutions on the 2-aminopyridine
ring compared with nitro substitution, with which the
reaction did not take place at all. This is most probably
because of strong electron withdrawing effect of nitro
substitution compared with halo substitutions or no sub-
stitution on 2-aminopyridine ring. The substitutions on
Baylis Hillman acetates were also influencing the reac-
tion yields with methoxy substitution or the phenoxy
substitution (entries 16 and 19, Table 1) resulting in the
products in 89% and 97% yield, respectively.
absorption in cmꢀ1
.
General procedure for synthesis of 3a–3s. A mixture of
Baylis Hillman acetate (2 mmol) and 2-aminopyridine (2
mmol) stirred at room temperature. The progress of the reac-
tion is monitored by TLC. After the completion of the reac-
tion, the solid product obtained was filtered off by triturating
with water. The white solid products collected were pure
enough for all practical purposes. Occasionally, some products
especially, substituted amino pyridines were washed with an
additional amount of water.
Spectral data of compounds 3.
3-Benzyl-2H-pyrido[1,2-a]pyrimidin-2-one (3a). White solid,
yield: 84%; m.p. 219–222ꢁC (decom.) [18]; IR (KBr): (mmax,
Condensation of Baylis Hillman acetate with 2-amino
pyridine may result in two different pyridopyrimidinone
structural frameworks, structure (A) or structure (B)
(Figure 2). Based on NMR studies, Basavaiah and
Satyanarayana assigned the condensation product as
structure A. To establish the structure unequivocally, we
have collected the X-ray diffraction data of single crys-
tal for 3l (entry 12) (Figure 3). The diffraction pattern
confirmed that the pyrido[1,2-a] pyrimidin-2-ones
formed by the condensation possess structure A, as
shown by earlier study.
cmꢀ1): 1650, 1602 cmꢀ1
;
1H-NMR (300 MHz, CDCl3
þ
DMSO-d6) d (ppm): 3.84 (2H, s, CH2), 6.74–6.78 (1H, t, Ar-
H, J ¼ 6.6 Hz), 7.21–7.30 (5H, m, Ar-H), 7.48–7.53 (1H, t,
Ar-H, J ¼ 7.3 Hz), 7.58 (1H, s, Ar-H), 7.70 (1H, s, Ar-H),
7.87–7.90 (1H, d, Ar-H, J ¼ 6.9 Hz); 13C-NMR (75 MHz,
DMSO-d6) d: 53.2, 129.6, 132.2, 142.1, 145.8, 147.1, 147.9
(2C), 148.4 (2C), 153.6, 155.9, 156.0, 158.3, 170.3; ESI Mass
(m/z) 237 (M þ Hþ); HRMS (EI): m/z Calculated value ¼
237.1027, Observed value ¼ 237.1039.
3-Benzyl-7-chloro-2H-pyrido[I,2-a]pyrimidin-2-one (3b). White
solid, yield: 71%; m.p. 236–239ꢁC (decom.); IR (KBr): (mmax,
cmꢀ1): 1655, 1616 cmꢀ1
;
1H-NMR (300 MHz, CDCl3
þ
A comparative study of both solvent-free and under
solvent reaction conditions [18] has been attempted to
demonstrate the superiority of the solvent-free protocol,
and the results are tabulated in Table 2. All reactions
occurred at room temperature. We found a definite
advantage of the solvent-free protocol especially in
terms of reaction time and yields.
DMSO-d6) d (ppm): 3.82 (2H, s, CH2) 7.18–7.21 (1H, d, Ar-
H, J ¼ 9.6 Hz), 7.28–7.29 (3H, m, Ar-H), 7.46–7.49 (1H, d,
Ar-H, J ¼ 9.6 Hz), 7.69 (2H, s, Ar-H), 7.85 (1H, s, Ar-H),
8.30 (1H, s, Ar-H); ESI Mass (m/z) 271 (Mþ); HRMS (EI): m/
z Calculated value ¼ 271.0638, Observed value ¼ 271.0633.
3-Benzyl-7-bromo-2H-pyrido[I,2-a]pyrimidin-2-one (3c). White
solid, yield: 68%; m.p. 237–240ꢁC (decom.); IR (KBr): (mmax,
cmꢀ1): 1653, 1616 cmꢀ1
DMSO-d6) d (ppm): 3.79 (2H, s, CH2), 7.10–7.13 (1H, d, Ar-
;
1H-NMR (300 MHz, CDCl3
þ
CONCLUSION
Scheme 1
To conclude, we have succeeded in simplifying the
important organic transformation of synthesis of substi-
tuted 2H-pyrido[1,2-a]pyrimidin-2-ones by avoiding sol-
vent usage in any stage of the protocol, thus making
this facile approach more versatile and green. Further,
the reaction occurs at room temperature without any
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Table 1
Synthesis of substituted 2H-pyrido[1,2-a]pyrimidin-2-one.
Entry
1
R1
H
R2
H
Product
Time
Yield* (%)
84
5 min
3a
3b
2
3
H
H
Cl
Br
4 h
5 h
71
68
3c
3d
3e
4
5
F
F
H
15 min
12 h
74
59
Cl
6
F
Br
16 h
58
3f
3g
3h
7
8
Cl
Cl
H
10 min
6 h
81
64
Cl
9
Cl
Br
6 h
63
3i
3j
10
11
Br
Br
H
10 min
3 h
86
70
Cl
3k
12
Br
Br
4 h
65
3l
3m
3n
13
14
CH3
CH3
H
10 min
14 h
82
59
Cl
15
CH3
Br
10 h
57
3o
3p
3q
16
17
OCH3
OCH3
H
8 min
6 h
89
60
Cl
18
19
20
OCH3
Br
H
15 h
15 min
72 h
59
97
-
3r
3s
3,5,6-trichloropyridin-2-yloxy
H
NO2
-
* Yields refer to isolated and pure compounds. All compounds gave spectral data consistent with their structures.

May 2011
A Solvent-Free Protocol for One Pot Conversion of Baylis Hillman Acetates to
Pyridopyrimidinones
589
Figure 2. Possible structure of pyridopyrimidinones formed.
H, J ¼ 9.4 Hz), 7.27–7.29 (3H, m, Ar-H), 7.56–7.60 (1H, d,
Ar-H, J ¼ 9.4 Hz), 7.87 (2H, s, Ar-H), 7.96 (1H, s, Ar-H),
8.47 (1H, s, Ar-H); ESI Mass (m/z) 315 (Mþ); HRMS (EI):
Figure 3. The molecular structure of 3l, with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 30% probability
level and H atoms are shown as small spheres of arbitrary radius.
m/z Calculated value
315.0123.
¼
315.0132, Observed value
¼
3-(4-Fluorobenzyl)-2H-pyrido[1,2-a]pyrimidin-2-one (3d). White
solid, yield: 74%; m.p. 220–224ꢁC (decom.); IR (KBr): (mmax,
(2H, t, Ar-H, J ¼ 8.6 Hz), 7.13–7.16 (1H, d, Ar-H, J ¼ 9.6
Hz), 7.27–7.31 (2H, dd, Ar-H, J ¼ 5.4 and 9.8 Hz), 7.53–7.56
(1H, dd, Ar-H, J ¼ 2.2 and 9.8 Hz), 7.88 (1H, s, Ar-H), 8.39
(1H, s, Ar-H); 13C-NMR (75 MHz, CDCl3-DMSO-d6) d: 33.3,
105.6, 115.3, 115.6, 119.1, 124.4, 128.1, 131.2, 131.3, 134.2,
134.8, 136.4, 139.3, 140.4, 143.3; ESI Mass (m/z) 333 (Mþ);
HRMS (EI): Calculated value ¼ 333.0038, Observed value ¼
333.0026.
cmꢀ1): 1654, 1585 cmꢀ1
;
1H-NMR (300 MHz, CDCl3
þ
DMSO-d6) d (ppm): 3.82 (2H, s, CH2), 6.73–6.78 (1H, t, Ar-
H), J ¼ 6.9 Hz), 6.96–7.01 (2H, t, Ar-H, J ¼ 8.6 Hz), 7.21–
7.24 (1H, d, Ar-H, J ¼ 8.8 Hz), 7.27–7.32 (2H, dd, Ar-H, J ¼
5.6 and 8.4 Hz), 7.47–7.53 (1H, t, Ar-H, J ¼ 8.1 Hz), 7.74
(1H, s, Ar-H), 7.90–7.92 (1H, d, Ar-H, J ¼ 6.7 Hz); 13C-NMR
(75 MHz, DMSO- d6) d: 52.2, 99.5, 132.3, 134.4, 134.7,
142.1, 147.0, 150.3, 150.4, 153.6, 154.3, 155.9, 156.1, 178.9,
182.1; ESI Mass (m/z) 255 (M þ Hþ); HRMS (EI): Calculated
value ¼ 255.0933, Observed value ¼ 255.0945.
3-(4-Chlorobenzyl)-2H-pyrido[1,2-a]pyrimidin-2-one (3g). White
solid, yield: 78%; m.p. 234–238ꢁC (decom.) [18]; IR (KBr):
;
(mmax, cmꢀ1): 1652, 1588 cmꢀ1 1H-NMR (300 MHz, CDCl3
þ DMSO-d6) d (ppm): 3.73 (2H, s, CH2), 6.76–6.79 (1H, t,
Ar-H, J ¼ 6.8 Hz), 7.11–7.13 (1H, d, Ar-H, J ¼ 8.7 Hz),
7.20–7.27 (3H, m, Ar-H), 7.50–7.53 (1H, t, Ar-H, J ¼ 7.8),
7.88 (1H, s, Ar-H), 8.03 (1H, s, Ar-H), 8.04–8.06 (1H, d, Ar-
H, J ¼ 6.8 Hz); ESI Mass (m/z) 271 (Mþ); HRMS (EI): m/z
Calculated value ¼ 271.0638, Observed value ¼ 271.0640.
3-(4-Chlorobenzyl)-7-chloro-2H-pyrido[1,2-a]pyrimidin-2-
one (3h). White solid, yield: 64%; m.p. 239–242ꢁC (decom.);
3-(4-Fluorobenzyl)-7-chloro-2H-pyrido[1,2-a]pyrimidin-2-
one (3e). White solid, yield: 59%; m.p. 240–243ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1656, 1598 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.82 (2H, s, CH2), 6.73–
6.78 (1H, t, Ar-H, J ¼ 7.1 Hz), 6.96–7.01 (2H, t, Ar-H, J ¼
8.6 Hz), 7.21–7.24 (1H, d, Ar-H, J ¼ 8.8 Hz), 7.27–7.32 (1H,
dd, Ar-H, J ¼ 5.6 and 8.4 Hz), 7.47–7.53 (1H, t, Ar-H, J ¼
8.8 Hz), 7.74 (1H, s, Ar-H), 7.90–7.92 (1H, d, Ar-H, J ¼ 6.7
Hz); ESI Mass (m/z) 289 (Mþ); HRMS (EI): m/z Calculated
value ¼ 289.0543, Observed value ¼ 289.0554.
IR (KBr): (mmax, cmꢀ1): 1655, 1617 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.77 (2H, s, CH2), 7.16–
7.19 (1H, d, Ar-H, J ¼ 9.6 Hz), 7.24–7.30 (4H, m, Ar-H),
7.50–7.53 (1H, d, Ar-H, J ¼ 9.6 Hz), 7.84 (1H, s, Ar-H), 8.01
(1H, s, Ar-H); ESI Mass (m/z) 305 (Mþ); HRMS (EI): m/z
Calculated value ¼ 305.0248, Observed value ¼ 305.0253.
3-(4-Fluorobenzyl)-7-bromo-2H-pyrido[1,2-a]pyrimidin-2-one
(3f). White solid, yield: 58%; m.p. 235–239ꢁC (decom.); IR
(KBr): (mmax, cmꢀ1): 1654, 1597 cmꢀ1 1H-NMR (300 MHz,
;
CDCl3 þ DMSO-d6) d (ppm): 3.79 (2H, s, CH2), 6.96–7.01
Table 2
Comparative study of solvent and solvent-free conditions for synthesis of substituted 2H-pyrido[1,2-a]pyrimidin-2-one.
MeOH:H2O (1:1)
Solvent Free Conditionsc
Product
R1
R2
Time (h)
Yield (%)
Time
Yield (%)
3a
3g
3m
3p
3b
3c
3h
3i
H
Cl
H
H
6a
6a
77
74
74
56
55
51
47
45
5 min
10 min
10 min
8 min
4 h
5 h
6 h
6 h
84
81
82
89
71
68
64
63
CH3
OCH3
H
H
Cl
H
H
6a
6a
Cl
Br
Cl
Br
24b
24b
24b
24b
Cl
a Reported by Basavaiah.
b Experiments carried in solvent system (MeOH:H2O) in our lab for comparision.
c Reactions done at our lab.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

590
R. Sreevani, A. Manjula, and B. V. Rao
Vol 48
H); 13C -NMR (75 MHz, DMSO-d6) d: 20.6, 32.2, 112.1,
115.1, 117.1, 123.8, 127.9, 128.8 (2C), 128.9 (2C), 133.7,
135.7, 138.8, 168.7; ESI Mass (m/z) 329 (Mþ); HRMS (EI):
Calculated value ¼ 329.0289, Observed value ¼ 329.0276.
3-(4-Methoxybenzyl)-2H-pyrido[1,2-a]pyrimidin-2-one
(3p). White solid, yield: 89%; m.p. 220–224ꢁC (decom.) [18];
3-(4-Chlorobenzyl)-7-bromo-2H-pyrido[1,2-a]pyrimidin-2-
one (3i). White solid, yield: 63%; m.p. 236–240ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1653, 1614 cmꢀ1 1H-NMR (500
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.75 (2H, s, CH2), 7.08–
7.10 (1H, d, Ar-H, J ¼ 9.7 Hz), 7.23 (4H, s, Ar-H), 7.51–7.53
(1H, d, Ar-H, J ¼ 11.7 Hz), 7.89 (1H, s, Ar-H), 8.41 (1H, s,
Ar-H); 13C -NMR (75 MHz, CDCl3-DMSO-d6) d: 33.7, 100.2,
112.6, 125.5, 127.9, 129.1 (2C), 130.9 (2C), 131.6, 134.2,
136.3, 138.6, 164.9, 171.3; ESI Mass (m/z) 349 (Mþ); HRMS
;
IR (KBr): (mmax, cmꢀ1): 1651, 1605 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.76 (2H, s, CH2), 3.77
(3H, s, CH3), 6.74–6.83 (3H, m, Ar-H), 7.18–7.22 (3H, m, Ar-
H), 7.48–7.54 (1H, t, Ar-H, J ¼ 6.9 Hz), 7.71 (1H, s, Ar-H),
7.93–7.95 (1H, d, Ar-H, J ¼ 6.6 Hz); ESI Mass (m/z) 267 (M
þ Hþ); HRMS (EI): m/z Calculated value ¼ 267.1133,
Observed value ¼ 267.1132.
(EI): Calculated value
348.9731.
¼
348.9743, Observed value
¼
3-(4-Bromobenzyl)-2H-pyrido[1,2-a]pyrimidin-2-one (3j). White
solid, yield: 86%; m.p. 238–241ꢁC (decom.); IR (KBr): (mmax,
cmꢀ1): 1652, 1586 cmꢀ1
;
1H-NMR (300 MHz, CDCl3
þ
3-(4-Methoxybenzyl)-7-chloro-2H-pyrido[1,2-a]pyrimidin-2-
one (3q). White solid, yield: 60%; m.p. 2220–225ꢁC (decom.);
DMSO-d6) d (ppm): 3.79 (2H, s, CH2), 6.75–6.80 (1H, t, Ar-
H, J ¼ 6.7 Hz), 7.04–7.07 (1H, d, Ar-H, J ¼ 8.3 Hz), 7.22–
7.28 (3H, t, Ar-H, J ¼ 8.3 Hz), 7.40–7.43 (2H, d, Ar-H, J ¼
8.3 Hz), 7.89 (1H, s, Ar-H), 8.00–8.02 (1H, d, Ar-H, J ¼ 6.0
Hz); ESI Mass (m/z) 315 (Mþ); HRMS (EI): m/z Calculated
value ¼ 315.0132, Observed value ¼ 315.0143.
IR (KBr): (mmax, cmꢀ1): 1654, 1600 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.72 (2H, s, CH2), 3.77
(3H, s, CH3), 6.80–6.83 (2H, d, Ar-H, J ¼ 8.1 Hz), 7. 17–7.19
(2H, d, Ar-H, J ¼ 7.3 Hz), 7.48–7.52 (1H, d, Ar-H, J ¼ 11.3
Hz), 7.83–7.86 (2H, d, Ar-H, J ¼ 9.2 Hz), 8.38 (1H, s, Ar-H);
13C -NMR (75 MHz, DMSO-d6) d: 32.8, 54.9, 101.2, 107.6,
113.2, 113.7 (2C), 123.8 (2C), 128.2, 130.0, 131.7, 135.7,
136.7, 149.2, 164.5; ESI Mass (m/z) 301 (Mþ); HRMS (EI):
Calculated value ¼ 301.0743, Observed value ¼ 301.0731.
3-(4-Methoxybenzyl)-7-bromo-2H-pyrido[1,2-a]pyrimidin-
2-one (3r). White solid, yield: 59%; m.p. 222–226ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1651, 1600 cmꢀ1; 1H-NMR (300 MHz,
CDCl3 þ DMSO-d6) d (ppm): 3.69 (2H, s, CH2), 3.75 (3H, s,
CH3), 6.80 (2H, s, Ar-H), 7.10 (1H, s, Ar-H), 7.18 (1H, s, Ar-
H), 7.63 (1H, s, Ar-H), 7.96 (1H, s, Ar-H), 8.02 (1H, s, Ar-H),
8.53 (1H, s, Ar-H); ESI Mass (m/z) 345 (Mþ); HRMS (EI): m/z
Calculated value ¼ 345.0238, Observed value ¼ 345.0244.
3-(4-(3,5,6-trichloropyridin-2-yloxy)benzyl)-2H-pyrido[1,2-
a]pyrimidin-2-one (3s). White solid, yield: 97%; m.p. 232–
3-(4-Bromobenzyl)-7-chloro-2H-pyrido[1,2-a]pyrimidin-2-
one (3k). White solid, yield: 70%; m.p. 240–242ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1655, 1615 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.78 (2H, s, CH2), 7.18–
7.22 (3H, m, Ar-H), 7.40–7.43 (2H, d, Ar-H, J ¼ 8.9 Hz),
7.46–7.49 (1H, d, Ar-H, J ¼ 9.8 Hz), 7.90 (1H, s, Ar-H), 8.35
(1H, s, Ar-H); ESI Mass (m/z) 349 (Mþ); HRMS (EI): m/z
Calculated value ¼ 348.9743, Observed value ¼ 348.9757.
3-(4-Bromobenzyl)-7-bromo-2H-pyrido[1,2-a]pyrimidin-2-
one (3l). White solid, yield: 65%; m.p. 239–240ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1652, 1615 cmꢀ1 1H-NMR (300
;
MHz, CDCl3 þ DMSO-d6) d (ppm): 3.78 (2H, s, CH2), 7.12–
7.15 (1H, d, Ar-H, J ¼ 9.8 Hz), 7.20–7.22 (2H, d, Ar-H, J ¼
8.0 Hz), 7.41–7.43 (2H, d, Ar-H, J ¼ 8.0 Hz), 7.54–7.57 (1H,
d, Ar-H, J ¼ 8.9 Hz), 7.67 (1H, s, Ar-H), 7.89 (1H, s, Ar-
H);ESI Mass (m/z) 394 (Mþ); HRMS (EI): m/z Calculated
value ¼ 394.9206, Observed value ¼ 394.9216.
236ꢁC (decom.); IR (KBr): (mmax, cmꢀ1): 1651, 1604 cmꢀ1
;
1H-NMR (300 MHz, CDCl3 þ DMSO-d6) d (ppm): 3.77 (2H,
s, CH2), 6.93–6.97 (1H, t, Ar-H, J ¼ 7.1 Hz), 7.13–7.17 (3H,
t, Ar-H, J ¼ 5.0 Hz), 7.37–7.40 (2H, d, Ar-H, J ¼ 8.3 Hz),
7.64–7.69 (1H, t, Ar-H, J ¼ 7.5 Hz), 8.15–8.18 (1H, d, Ar-H,
J ¼ 7.3 Hz), 8.30 (1H, s, Ar-H), 8.53 (1H, s, Ar-H); ESI Mass
3-(4-Methylbenzyl)-2H-pyrido[1,2-a]pyrimidin-2-one
(3m). White solid, yield: 82%; m.p. 232–234ꢁC (decom.)
1
[18]; IR (KBr): (mmax, cmꢀ1): 1649, 1600 cmꢀ1; H-NMR (300
(m/z) 432 (Mþ); HRMS (EI): m/z Calculated value
432.1023, Observed value ¼ 432.1024.
¼
MHz, CDCl3 þ DMSO-d6) d (ppm): 2.32 (3H, s, CH3), 3.77
(2H, s, CH2), 6.75–6.77 (1H, t, Ar-H, J ¼ 6.3 Hz), 7.07–7.20
(5H, m, Ar-H), 7.49–7.52 (1H, t, Ar-H, J ¼ 8.1 Hz), 7.77 (1H,
s, Ar-H), 7.94–7.96 (1H, d, Ar-H, J ¼ 7.2 Hz); ESI Mass (m/
z) 251 (M þ Hþ); HRMS (EI): m/z Calculated value ¼
251.1184, Observed value ¼ 251.1195.
Structural data of 3l. X-ray data for the compound 3l were
collected at room temperature using a Bruker Smart Apex
CCD diffractometer with graphite monochromated MoKa radi-
˚
ation (k¼ 0.71073 A) with x-scan method. Preliminary lattice
parameters and orientation matrices were obtained from four
sets of frames. Unit cell dimensions were determined from the
setting angles of 6092 reflections for (3l).
3-(4-Methylbenzyl)-7-chloro-2H-pyrido[1,2-a]pyrimidin-2-
one (3n). White solid, yield: 59%; m.p. 233–236ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1655, 1616 cmꢀ1 1H-NMR (300
;
Integration and scaling of intensity data were accomplished
using SAINT program. The structures were solved by Direct
Methods using SHELXS97 and refinement was carried out by
full-matrix least-squares technique using SHELXL97. Aniso-
tropic displacement parameters were included for all non-
hydrogen atoms. All the H atoms were positioned geometri-
cally and treated as riding on their parent C atoms, with CAH
MHz, CDCl3 þ DMSO-d6) d (ppm): 2.31 (3H, s, CH2), 3.73
(2H, s, CH2), 7.06–7.18 (5H, m, Ar-H), 7.52–7.55 (1H, dd, Ar-
H, J ¼ 2.2 and 9.6 Hz), 7.96 (1H, s, Ar-H), 8.42–8.43 (1H, d,
Ar-H, J ¼ 1.8 Hz); ESI Mass (m/z) 285 (Mþ); HRMS (EI): m/z
Calculated value ¼ 285.08 14, Observed value ¼ 285.0822.
3-(4-Methylbenzyl)-7-bromo-2H-pyrido[1,2-a]pyrimidin-2-
one (3o). White solid, yield: 57%; m.p. 234–238ꢁC (decom.);
IR (KBr): (mmax, cmꢀ1): 1652, 1609 cmꢀ1 1H-NMR (300
;
˚
distances of 0.93–0.97 A, and with Uiso(H) ¼ 1.2Ueq(C) for
other H atoms. CCDC-760517 contains the supplementary
crystallographic data for this article. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
MHz, CDCl3 þ DMSO-d6) d (ppm): 2.32 (3H, s, CH3), 3.74
(2H, s, CH2), 7.07–7.09 (2H, d, Ar-H, J ¼ 8.3 Hz), 7.13–7.16
(2H, d, Ar-H, J ¼ 8.1 Hz), 7.56–7.59 (1H, d, Ar-H, J ¼ 9.6
Hz), 7.86–7.89 (2H, d, Ar-H, J ¼ 10.3 Hz), 8.45 (1H, brs, Ar-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
A Solvent-Free Protocol for One Pot Conversion of Baylis Hillman Acetates to
Pyridopyrimidinones
591
[7] Bookser, B. C.; Ugarkar, B. G.; Matelich, M. C.; Lemus, R.
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B.; Erion, M. D. J Med Chem 2005, 48, 7808.
Acknowledgments. The authors thank Dr. Ravi Kumar and Dr.
B. Sridhar, X-ray Crystallography Division, IICT for X-ray struc-
ture. RS would like to thank UGC (New Delhi) for the Research
Fellowship and the authors’ wishes to thank Director, IICT for
the support.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet