Synthesis of fused pyrimidines from amines and cyclic β-formylesters

Article abstract of DOI:10.1016/j.tet.2007.05.123

A highly efficient method was successfully developed for the synthesis of fused pyrimidines via aminoheterocyclic dihydrofuranone intermediates obtained from 2-aminoheterocycles and cyclic β-formylesters by three different methods.

Full text of DOI:10.1016/j.tet.2007.05.123

Tetrahedron 63 (2007) 8157–8163
Synthesis of fused pyrimidines from amines
and cyclic b-formylesters
*
Raghunath B. Toche, Bhausaheb K. Ghotekar, Muddassar A. Kazi,
Dhananjay B. Kendre and Madhukar N. Jachak
Organic Chemistry Research Centre, Department of Chemistry, K.T.H.M. College,
Gangapur Road, Nashik 422002, Maharashtra, India
Received 5 March 2007; revised 15 May 2007; accepted 31 May 2007
Available online 6 June 2007
Abstract—A highly efficient method was successfully developed for the synthesis of fused pyrimidines via aminoheterocyclic dihydrofur-
anone intermediates obtained from 2-aminoheterocycles and cyclic b-formylesters by three different methods.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
condensed 2-aminoheterocyclics with cyclic b-formylesters,
i.e., sodium salt of a-formyl-g-butyrolactone 1a or a-ethoxy-
ethylidene-g-butyrolactone 2a to obtain pyrimidines with
a 3-chloroethyl side chain and the pyrimidines having a
3-chloropropyl side chain (Fig. 1).
Benzo- and hetero-fused pyrimidines are known to exhibit
promising antiviral,1 antibacterial,2 anti-AIDS,3 and antino-
ciceptive4 activities. Fused pyrimidines are selective inhibi-
tors for multidrug resistance (MDR).5 Folate metabolism
has long been recognized as an attractive target for cancer
chemotherapy because of the indispensable role of fused
pyrimidine antifolates as antitumor agents.6 Atherothrom-
botic coronary artery disease, giving rise to a number of car-
dio circulatory disorders such as myocardial infarction (MI),
unstable angina (UA), or acute stroke associated with deep
vein thrombosis (DVT), is one of the most important causes
of death worldwide. The relevance of fused pyrimidines
as antiplatelet and antithrombotic drugs7 has been firmly
established by clinical trials. Thus, further exploration of
pyrimidine chemistry appears to be worthwhile.
O X
H
1a, R = H; 1b, R = CH3; X = Na+
2a, R = H; 2b, R = CH3; X = C2H5
O
R
O
1a-b, 2a-b
Figure 1.
2. Results and discussion
Synthesis of new pyrido[1,2-a]pyrimidin-4-(1H)-ones 5a–f
and benzohetero[3,2-a]pyrimidin-4(1H)-ones 8a–h was ob-
tained through aminoheterocyclic dihydrofuranones 4a–f,
7a–h as key intermediates (Scheme 1).
Our ongoing interest in pyrimidine synthesis8–11 and modifi-
cations to the Pechmann12 reaction prompted us to develop
a facile synthetic method for fused pyrimidines. Fused pyrim-
idineshaving2-methyland 3-chloro/hydroxyethyl-sidechain
are found to be biologically important compounds,13–17 and
were obtained from a-acetyl-g-butyrolactone and 2-amino-
heterocycles. However, mixture of products were observed
in these cases17 and the intermediates were not isolated.
In the first method (Method A), the sodium salt of a-formyl-
g-butyrolactone 1a or sodium salt a-formyl-g-valerolactone
1b was condensed with 2-aminopyridines 3a–c in toluene
and catalytic p-toluenesulfonic acid. The electrophilic for-
myl group is generated by protonation of 1a, which reacts
with –NH2 to furnish aminoheterocyclic-4,5-dihydrofuran-
2(3H)-ones 4a–f in 65–70% yield.
In the present study, we report the synthesis of fused pyrim-
idines with 3-chloroethyl/chloropropyl side chain and the
absence of a 2-methyl group. For this purpose, we have
In the second method (Method B), the condensation of 1a or
1b with 2-aminopyridines 3a–c was carried out using ammo-
nium acetate at 120 ꢀC for 1 h to furnish 4a–f in 70–75%
yield (Scheme 1).
Keywords: Aminoheterocyclic dihydrofuranone; a-Formyl-g-butyrolac-
tone; Fused pyrimidines; Ammonium acetate.
* Corresponding author. Tel.: +91 253 2582876; fax: +91 253 2577341;
e-mail: raghunath_toche@rediffmail.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.123

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R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
R
R
O
O
O
N
O
Cl
O
N
N
N
N
H
H
R
N
H
NH2
3a-c,6a-d
N
5a-f,8a-h
H
4a-f,7a-h
R3
N
NH
NH2
=
N
N
N
N
NH2
;
R2
NH2
O
NH2;
S
NH ;
MeO
2
S
NH2;
S
R1
3a-c
6a
6b
6c
6d
Scheme 1. Method A: toluene/p-TsOH; Method B: NH4OAc/120 ꢀC; Method C: CH2Cl2/rt.
The NH+4 reacts with the sodium salt of lactone 1a or 1b to
furnish the a-formyl lactones in situ and the evolved ammo-
nia can bring out condensation between –NH2 and the
formyl group of the lactone. This method gives higher yield
(70–72%) and required a shorter time (1 h) than Method
A. The ammonium acetate is easily available and non-
hazardous and the aqueous work-up of the reaction made
product isolation simple. Therefore, it may be useful for
large-scale synthesis of enamines. In the third method
(Method C), the intermediate products 4a–f were obtained
by stirring 2-aminopyridines 3a–c with a-ethoxyethylene-
g-butyrolactone 2a or a-ethoxyethylene-g-valerolactone
2b in dichloromethane at room temperature. Method C gives
higher yields of 4a–f (70–75%) at room temperature and the
solvent used can be recycled after isolation of the products.
But it is an inconvenient method as the preparation of 2a or
2b required stoichiometric amounts of ethylchloroformate,
which is a lachrymator and cannot be used commercially.
The results are tabulated in Table 1.
completed in a short time (Scheme 1). The results are tabu-
lated in Table 1. The structures of 5a–f were elucidated by IR
and NMR spectroscopies, mass spectrometry and elemental
analysis.
Our interest in this area was sparked by the unexpected re-
sults obtained with 2-aminopyridines 3a–c by Method B and
prompted us to generalize the use of ammonium acetate.
We have selected 2-aminoheterocycles containing sulfur,
oxygen, and nitrogen as heteroatoms. Thus, 2-aminobenzo-
thiazole 6a, 2-amino-6-methoxybenzothiazole 6b, 2-amino-
benzoxazole 6c, and 2-aminothiazole 6d were reacted with
lactones 1a,b, 2a,b by Methods A, B, and C as discussed
earlier. With heterocycles 6a–h, it was observed that
Method A (p-TsOH/toluene) gave higher yield (66–73%)
than Method B (48–65%). Hence, Method A is the most use-
ful for the synthesis of aminoheterocyclic dihydrofuranones
7a–h. The reduction in yields were due to the formation of
a salt between 2-aminoheterocycles 6a–h and ammonium
acetate used in excess. The salt formed with p-TsOH did
not affect the yields of 7a–h as it was used in small amounts.
This type of salt was not observed in case of 3a–c with
ammonium acetate.
1
The new compounds 4a–f were characterized by IR, H
NMR, and 13C NMR spectroscopies and elemental analysis.
In the IR spectrum of 4a, the C]O resonance was at
1718 cmꢁ1 due to intermolecular hydrogen bonding be-
tween –NH and –CO.
The key intermediates, 7a–h, were cyclized using phos-
phorous oxychloride to fused pyrimidines 8a–h. The reac-
tions proceeded smoothly and gave facile ring closure
reaction to furnish fused pyrimidines 8a–h in 60–70%
yields as single products (Scheme 1). The results are
The key intermediates, 4a–f, were cyclized using phospho-
rous oxychloride to pyrido[1,2-a]pyrimidin-4(1H)-one 5a–f
in 60–70% yield. The reactions were smooth and
Table 1. Comparative % yields of aminoheterocyclic dihydrofuranone 4a–f, 7a–h by Method A, B, and C and % yield of fused pyrimidines 5a–f, 8a–h
Amine
R
R1
R2
R3
Aminoheterocyclic
dihydrofuranone
Method A,
PTSA/Toluene
Method B,
NH4OAc
Method C,
rt, CH2Cl2
Fused
pyrimidine
% Yield
3a
3b
3c
3a
3b
3c
6a
6a
6b
6b
6c
6c
6d
6d
H
H
H
H
H
H
H
H
H
—
—
—
—
—
—
—
—
H
CH3
H
H
CH3
H
—
—
—
—
—
—
—
—
H
H
CH3
H
H
CH3
—
—
—
—
—
—
—
—
4a
4b
4c
4d
4e
4f
7a
7b
7c
7d
7e
7f
65
68
70
69
68
65
70
70
70
70
61
62
65
60
70
71
72
70
69
69
63
62
66
64
48
48
49
48
71
71
72
68
69
70
70
74
70
71
55
52
49
47
5a
5b
5c
5d
5e
5f
8a
8b
8c
8d
8e
8f
78
78
65
65
64
63
60
66
70
60
61
60
65
62
CH3
CH3
CH3
H
CH3
H
CH3
H
CH3
H
7g
7h
8g
8h
CH3

R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
8159
R
O
O
Method A , B
Method A , B
N
N
H
H
N
N
H
10 a-b
+
1a-b
Cl
N
NH2
N
H
O
Cl
OH
N
9
POCl3
N
R
R
N
N
H
N
11 a-b
12
Scheme 2. Method A: toluene/PTSA; Method B: NH4OAc; Method C: CH2Cl2/rt.
tabulated in Table 1. IR and NMR spectroscopies and
elemental analysis were used to characterize the com-
pounds 8a–h.
(Merck) plates using UV light (254 and 366 nm) for detec-
tion. Column chromatography was carried out on silica gel
(SD Fine Chemicals, 60–80 mesh). Starting materials were
obtained from commercial suppliers and used without
further purification. Common reagent-grade chemicals
were either commercially available and used without further
purification or prepared by standard literature procedures.
We have made an interesting observation in the condensa-
tion of 2-aminobenzoimidazole 9 with the sodium salt of
lactone 1a or 1b. Either Method A (p-TsOH/toluene) or
Method B (NH4OAc) did not afford aminoheterocyclic di-
hydrofuranones 10a,b, but gave cyclized products 3-(2-hy-
droxyethyl)-1,3-benzimidazolo[3,2-a]pyrimidin-4(1H)-one
11a and 3-(2-hydroxypropyl)-1,3-benzimidazolo[3,2-a]pyr-
imidin-4(1H)-one 11b in 70% yield. The intermediates
10a,b are presumably unstable due to the higher basicity of
2-aminobenzoimidazole 9. Compound 11a on refluxing in
phosphorous oxychloride yielded the corresponding chloro-
derivatives 12. All these compounds were characterized by
1H NMR and IR spectroscopies and elemental analysis
(Scheme 2). The neat reaction of lactone 1a,b or 2a,b with
2-aminoheterocycles 3a–c or 6a–h or with 9 yielded mixture
of several products.
4.2. Synthesis of 4,5-dihydrofuranone intermediates
4.2.1. 3-[(2-Pyridylamino)-methylidene]-4,5-dihydro-
furan-2-(3H)-one (4a–f), (7a–h) (Method A). A mixture
of 2-aminopyridines 3a–c, 6a–d (0.01 mol) and sodium
salt of a-formyl-g-butyrolactone 1a or sodium salt of a-for-
myl-g-valerolactone 1b (0.01 mol) in toluene (20 mL) con-
taining catalytic amount (0.020 g) of p-toluenesulfonic acid
was refluxed for 8 h. The solvent was evaporated in vacuum
and the remaining solid was stirred with water (30 mL),
filtered, dried, and recrystallized.
4.2.2. 3-[(2-Pyridylamino)-methylidene]-4,5-dihydro-
furan-2-(3H)-one (4a–f), (7a–h) (Method B). A mixture
of 2-aminopyridines 3a–c, 6a–d (0.01 mol) and sodium
salt of a-formyl-g-butyrolactone 1a or sodium salt of a-
formyl-g-valerolactone 1b (0.01 mol) in ammonium acetate
(0.05 mol) was heated under Vigreux column at 120 ꢀC for
1 h. Cold water (30 mL) was added to viscous reaction mix-
ture and was stirred for 30 min to remove the excess of am-
monium acetate. The precipitated solid product was filtered,
washed with water, dried, and recrystallized.
3. Conclusion
The methodology is useful to prepare fused pyrimidines with
a 3-chloroethyl or a 3-chloropropyl side chain in high yield.
The sodium salt of cyclic b-formylester can directly react
with 2-aminoheterocycles in ammonium acetate or in
p-TsOH/toluene to yield enamine intermediates. The limita-
tions of the methods with 2-amino-N-heterocycles having
heteroatom a to amine group were also discussed.
4.2.3. 3-[(2-Pyridylamino)-methylidene]-4,5-dihydro-
furan-2-(3H)-one (4a–f), (7a–h) (Method C). A mixture
of 2-aminopyridines 3a–c, 6a–d (0.01 mol) and a-ethoxy-
ethylidene-g-butyrolactone 2a or a-ethoxyethylidene-
g-valerolactone 2b (0.01 mol) in dichloromethane (30 mL)
was stirred for 1.5 h. The solvent was evaporated in vacuum.
The solid product was isolated and recrystallized.
4. Experimental
4.1. General
Melting points were determined on a Gallenkamp melting
point apparatus in open capillary tubes and are uncorrected.
The 1H and 13C NMR spectra were recorded on a Varian XL-
300 spectrometer (300 MHz). Chemical shifts are reported
in parts per million from internal tetramethylsilane standard
and are given in d units. The solvent for NMR spectra were
taken in deuteriochloroform, DMSO-d6. Infrared spectra
were taken on a Shimadzu FTIR-408 in potassium bromide
pellets unless otherwise stated. The mass spectrum was re-
corded on QP-2010s. Elemental analyses were performed
on a Hosli CH-Analyzer and are within ꢂ0.4 of the theoret-
ical percentages. All reactions were monitored by thin layer
chromatography, carried out on 0.2 mm silica gel 60 F254
4.3. Synthesis of fused pyrido[1,2-a]pyrimidin-4-(1H)-one
4.3.1. 3-(2-Chloroethyl)/-3-(2-chloropropyl)pyrido[1,2-
a]pyrimidin-4-(1H)-one (5a–f). A mixture of 4a–f or
(0.01 mol) and phosphorous oxychloride (30 mL) was re-
fluxed for 2 h. The excess of phosphorous oxychloride was
evaporated using rotary evaporator under reduced pressure.
The ice-cold water (100 mL) was added to the reaction mix-
ture, neutralized with solid sodium carbonate (6 g), and fur-
ther stirred for 24 h. The precipitated product was filtered,
washed with water, dried, and recrystallized.

8160
R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
4.4. General procedure for the synthesis of 8a–h
J¼7.0 Hz, 1H, C5–H), 7.45 (t, J¼7.0 Hz, 1H, C4–H), 8.12
(dt, J¼12, 1.6 Hz, 1H, ]C–H), 9.62 (d, J¼12.0 Hz, 1H,
NH). Anal. Calcd for C11H12N2O2: C, 64.69; H, 5.92; N,
13.72. Found: C, 64.70; H, 5.91; N, 13.65.
A mixture of 7a–h (0.01 mol), phosphorous oxychloride
(30 mL), and toluene (10 mL) was refluxed for 2 h. The ex-
cess of phosphorous oxychloride and toluene was evapo-
rated using rotary evaporator under reduced pressure. The
ice-cold water (100 mL) was added to the reaction mixture,
neutralized with solid sodium carbonate (6 g), and further
stirred for 24 h. The precipitated product was filtered,
washed with water, dried, and recrystallized.
4.5.6. 3-[2-(2-Pyridylamino)-methylidene]-5-methyl-4,5-
dihydrofuran-2(3H)-one (4d). Recrystallized from meth-
anol as colorless needles: mp 175 ꢀC; IR (KBr): 3300,
1
1720, 1660, 1630, 1600, 1580, 1480, 1420 cmꢁ1. H NMR
(CDCl3): d 1.36 (d, J¼8.0 Hz, 3H, CHCH3), 2.36, 2.96 (qd,
dq, J¼2.1, 5.9, 7.5 Hz, 2H, –CH2), 4.67 (m, 1H, CHCH3),
6.92 (m, 2H, C4–H, C5–H), 7.73 (d, J¼7.0 Hz, 1H, C3–H),
7.95 (d, J¼12.0 Hz, 1H, NH exchangeable with D2O),
8.24 (d, J¼7.0 Hz, 1H, C6–H), 8.32 (dt, J¼12.0, 1.7 Hz,
1H, ]C–H). Anal. Calcd for C11H12N2O2: C, 64.69; H,
5.92; N, 13.72. Found: C, 64.66; H, 5.91; N, 13.67.
4.5. Synthesis of benzimidazolo[3,2-a]pyrimidin-
4(1H)-one
4.5.1. 3-(2-Hydroxyethyl)-1,3-benzimidazolo[3,2-a]pyr-
imidin-4(1H)-one (11a,b) (Method A). A mixture of
2-aminobenzoimidazole 9 (0.01 mol) and sodium salt of
a-formyl-g-butyrolactone 1a or sodium salt of a-formyl-
g-valerolactone 1b (0.01 mol) was reacted and work-up as
described in Section 4.2.1.
4.5.7. 3-[2-(4-Methyl-2-pyridylamino)-methylidene]-5-
methyl-4,5-dihydrofuran-2(3H)-one (4e). Recrystallized
from acetonitrile as colorless needles: mp 190–191 ꢀC;
IR (KBr): 3230, 2910, 1730, 1670, 1610, 1600, 1570,
4.5.2. 3-(2-Chloroethyl)-pyrido[1,2-a]pyrimidin-4-(1H)-
one (12a). A mixture of 11a (0.01 mol) and phosphorous
oxychloride (30 mL) was refluxed for 3 h. The excess of
phosphorous oxychloride was evaporated using rotary evap-
orator under reduced pressure. The ice-cold water (100 mL)
was added to the reaction mixture, neutralized with solid
sodium carbonate (6 g), and further stirred for 24 h. The pre-
cipitated product was filtered, washed with water, dried, and
recrystallized.
1480 cmꢁ1
.
1H NMR (CDCl3): d 1.41 (d, J¼8 Hz, 3H,
CH–CH3), 2.35 (s, 3H, C4–CH3), 2.45, 3.05 (qd, dq,
J¼2.1, 5.9, 7.5 Hz, 2H, –CH2), 4.67 (m, 1H, CHCH3),
6.82 (d, J¼7.0 Hz, 1H, C5–H), 6.91 (s, 1H, C3–H), 7.88
(d, J¼12.0 Hz, 1H, NH exchangeable with D2O), 8.22
(dt, J¼12.0, 1.7 Hz, 1H, ]C–H), 8.24 (d, J¼7.0 Hz, 1H,
C6–H). Anal. Calcd for C12H14N2O2: C, 66.04; H, 6.47;
N, 12.84. Found: C, 66.58; H, 6.70; N, 12.65.
4.5.8. 3-[2-(6-Methyl-2-pyridylamino)-methylidene]-5-
methyl-4,5-dihydrofuran-2(3H)-one (4f). Recrystallized
from methanol as colorless needles: mp 156–157 ꢀC; IR
(KBr): 3230, 3120, 2960, 1720, 1680, 1640, 1600, 1580,
4.5.3. 3-[2-(2-Pyridylamino)-methylidene]-4,5-dihydro-
furan-2-(3H)-one (4a). Recrystallized from acetonitrile as
colorless needles: mp 216–216 ꢀC; IR (KBr): 3290, 1718,
1
1
1660, 1636, 1605, 1576, 1502, 1472, 1414 cmꢁ1. H NMR
1520, 1450 cmꢁ1. H NMR (CDCl3): d 1.36 (d, J¼8.0 Hz,
(DMSO-d6): d 2.95 (dt, J¼7.0, 1.6 Hz, 2H, –CH2), 4.35 (t,
J¼7.0 Hz, 2H, –CH2O), 6.92 (m, 2H, C4–H, C5–H), 7.73
(d, J¼7.0 Hz, 1H, C3–H), 8.24 (d, J¼7.0 Hz, 1H, C6–H),
8.32 (dt, J¼12.0, 1.6 Hz, 1H, ]C–H), 9.76 (d, J¼12.0 Hz,
1H, NH). 13C NMR (DMSO-d6): d 26.2, 35.6, 93.6, 113.9,
117.5, 137.6, 147.8, 152.4, 153.5, 173.7. Anal. Calcd for
C10H10N2O2: C, 63.15; H, 5.30; N, 14.73. Found: C,
63.19; H, 5.38; N, 14.73.
3H, C6–CH3), 1.38 (d, J¼8.0 Hz, 3H, CH–CH3), 2.45,
3.05 (qd, dq, J¼2.1, 5.9, 7.5 Hz, 2H –CH2), 4.75 (m, 1H,
C5–H), 6.65 (d, J¼7.0 Hz, 1H, C3–H), 6.78 (d, J¼7.0 Hz,
1H, C5–H), 7.45 (t, J¼7.0 Hz, 1H, C4–H), 7.99 (d, J¼
12.0 Hz, 1H, NH exchangeable with D2O), 8.15 (dt, J¼12.0,
1.7 Hz, 1H, ]C–H). Anal. Calcd for C12H14N2O2: C,
66.04; H, 6.47; N, 12.84. Found: C, 66.12; H, 6.68; N, 12.86.
4.5.9. 3-(2-Chloroethyl)-pyrido[1,2-a]pyrimidin-4(1H)-
one (5a). Recrystallized from ligroin as colorless needles:
mp 109–111 ꢀC; IR (KBr): 2980, 1660, 1630, 1580, 1530,
4.5.4. 3-[2-(4-Methyl-2-pyridylamino)methylidene]-4,5-
dihydrofuran-2(3H)-one (4b). Recrystallized from N,N-
dimethylformamide/ethanol (7:3) as colorless needles: mp
233–234 ꢀC; IR (KBr): 3300, 1720, 1660, 1630, 1610,
1570, 1520, 1480, 1440 cmꢁ1. 1H NMR (DMSO-d6): d 2.34
(s, 3H, C3–CH3), 2.90 (dt, J¼7.0, 1.6 Hz, 2H, –CH2), 4.36 (t,
J¼7.0 Hz, 2H, –CH2O), 6.82 (d, J¼7.0 Hz, 1H, C5–H), 7.73
(s, 1H, C3–H), 8.24 (d, J¼7.0 Hz, 1H, C6–H), 8.12 (dt,
J¼12.0, 1.6 Hz, 1H, ]C–H), 9.76 (d, J¼12.0 Hz, 1H,
NH). Anal. Calcd for C11H12N2O2: C, 64.69; H, 5.92; N,
13.72. Found: C, 64.54; H, 6.03; N, 13.84.
1
1500, 1450 cmꢁ1. H NMR (CDCl3): d 3.15 (t, J¼7.0 Hz,
2H, CH2), 3.85 (t, J¼7.0 Hz, 2H, CH2Cl), 7.15 (dt, J¼7.0,
1.7 Hz, 1H, C8–H), 7.75 (m, 2H, C9–H & C7–H), 8.35 (s,
1H, C2–H), 9.05 (d, J¼7.0 Hz, 1H, C6–H). 13C NMR:
d 26.5, 62.5, 111.4, 127.0, 135.3, 148.3, 157.8, 162.4,
171.0. Anal. Calcd for C10H9ClN2O: C, 57.57; H, 4.35; N,
13.43. Found: C, 57.25; H, 4.80, N. 13.51.
4.5.10. 3-(2-Chloroethyl)-8-methyl-pyrido[1,2-a]pyrimi-
din-4(1H)-one (5b). Recrystallized from ligroin as colorless
needles: mp 108–109 ꢀC; IR (KBr): 2980, 1670, 1640, 1580,
4.5.5. 3-[2-(6-Methyl-2-pyridylamino)-methylidene]-4,5-
dihydrofuran-2(3H)-one (4c). Recrystallized from N,N-
dimethylformamide/ethanol (8:2) as colorless needles: mp
207–208 ꢀC; IR (KBr): 3380, 1720, 1660, 1630, 1600, 1580,
1480, 1440 cmꢁ1. 1H NMR (DMSO-d6): d 2.43 (s, 3H, C6–
CH3), 2.90 (dt, J¼7.0, 1.6 Hz, 2H, –CH2), 4.36 (t, J¼7.0 Hz,
2H, OCH2), 6.62 (d, J¼7.0 Hz, 1H, C3–H), 6.84 (d,
1
1500, 1450, 1440 cmꢁ1. H NMR (CDCl3): d 2.51 (s, 3H,
C8–Me), 3.05 (t, J¼7.0 Hz, 2H, CH2), 3.88 (t, J¼7.0 Hz,
2H, CH2Cl), 7.15 (dd, J¼7.0 Hz, 1H, C7–H), 7.45 (s, 1H,
C9–H), 8.25 (s, 1H, C2–H), 8.95 (d, J¼7.0 Hz, 1H, C6–H).
Anal. Calcd for C11H11ClN2O: C, 59.33; H, 4.98; N, 12.58;
Cl, 15.92. Found: C, 59.19; H, 4.89, N, 12.50; Cl, 15.77.

R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
8161
4.5.11. 3-(2-Chloroethyl)-6-methyl-pyrido[1,2-a]pyrim-
idin-4(1H)-one (5c). Recrystallized from cyclohexane as
colorless needles: mp 89–90 ꢀC; IR (KBr): 2900, 1670,
1440 cmꢁ1. 1H NMR (DMSO-d6): d 1.45 (d, J¼7.0 Hz, 3H,
CH3), 2.42, 3.15 (qd, dq, J¼2.1, 5.9, 7.5 Hz, 2H, CH2), 4.78
(m, 1H, CH–Me), 7.25 (dd, J¼8.0, 2.0 Hz, 1H, C7–H), 7.35
(dd, J¼8.0, 2.0 Hz, 1H, C4–H), 7.72 (dt, J¼8.0, 2.0 Hz, 1H,
C5–H), 7.85 (dt, J¼8.0, 2.0 Hz, 1H, C6–H), 7.95 (dt, J¼12.0,
3.0 Hz, 1H, ]CH), 10.85 (br s, 1H, NH). Anal. Calcd for
C13H12N2O2S: C, 59.98; H, 4.65; N, 10.76. Found: C,
60.12; H, 4.41; N, 10.80.
1
1630, 1480, 1440 cmꢁ1. H NMR (CDCl3): d 2.50 (s, 3H,
C6–CH3), 3.10 (t, J¼7.0 Hz, 2H, CH2), 3.87 (t, J¼7.0 Hz,
2H, CH2Cl), 6.75 (m, 1H, C7–H), 7.40 (dd, J¼7.0 Hz, 1H,
C8–H), 8.20 (s, 1H, ]CH), 8.95 (d, J¼8.0 Hz, 1H, C9–H).
Anal. Calcd for C11H11ClN2O: C, 59.33; H, 4.98; N, 12.58;
Cl, 15.92. Found: C, 59.14; H, 5.02, N, 12.34; Cl, 15.80.
4.5.17. 6-Methoxy-2-[1-(2-oxo-2,3,4,5-tetrahydrofuran-
3-yl)-ethen-2-yl-amino]-1,3-benzothiazole (7c). Recrys-
tallized from N,N-dimethylformamide/ethanol (8:2) as
pale yellow needles: mp 254–255 ꢀC; IR (KBr): 3280,
4.5.12. 3-(2-Chloropropyl)-pyrido[1,2-a]pyrimidin-
4(1H)-one (5d). Recrystallized from cyclohexane as color-
less needles: mp 91–92 ꢀC; IR (KBr): 2900, 1670, 1630,
1
1
1480, 1440 cmꢁ1. H NMR (CDCl3): d 1.65 (d, J¼7.0 Hz,
3020, 1725, 1670, 1630, 1600, 1540, 1470 cmꢁ1. H NMR
3H, CH3), 3.85, 3.15 (q, dd, J¼3.0, 6.0, 8.0 Hz, 2H, CH2),
4.45 (m, 1H, CHCH3), 7.15 (dt, J¼7.0, 2.0, 9.0 Hz, 1H,
C8–H), 7.75 (d, J¼8.0 Hz, 2H, C9–H, C7–H), 8.25 (s, 1H,
]CH), 9.05 (d, J¼7.0 Hz, 1H, C6–H). Anal. Calcd for
C11H11ClN2O: C, 59.33; H, 4.98; N, 12.58; Cl, 15.92.
Found: C, 59.15 H, 5.03, N, 12.34; Cl, 15.95.
(DMSO-d6): d 2.95 (dt, J¼7.0, 3.0 Hz, 2H, –CH2), 3.82 (s,
3H, OCH3), 4.42 (t, J¼7.0 Hz, 2H, CH2), 7.02 (d,
J¼2.0 Hz, 1H, C7–H), 7.55 (d, J¼8.0 Hz, 1H, C4–H), 7.64
(dt, J¼8.0, 2.0 Hz, 1H, C5–H), 8.05 (dt, J¼12.0, 3.0 Hz,
1H, ]C–H), 11.8 (d, J¼12 Hz, 1H, NH). Anal. Calcd for
C13H12N2O3S: C, 56.51; H, 4.38; N, 10.14; S, 11.60. Found:
C, 56.36; H, 4.25; N, 10.17; S, 11.36.
4.5.13. 3-(2-Chloroethyl)-8-methyl-pyrido[1,2-a]pyrimi-
din-4(1H)-one (5e). Recrystallized from ligroin as colorless
needles: mp 137–138 ꢀC; IR (KBr): 3020, 2990, 1670, 1640,
4.5.18. 6-Methoxy-2-[1-(5-methyl-2-oxo-2,3,4,5-tetrahy-
drofuran-3-yl)-ethen-2-yl-amino]-1,3-benzothiazole
(7d). Recrystallized from methanol as colorless needles: mp
236–237 ꢀC; IR (KBr): 3190, 2990, 2910, 1725, 1640, 1600,
1
1580, 1450 cmꢁ1. H NMR (CDCl3): d 1.5 (d, J¼8.0 Hz,
3H, CH3), 2.45 (s, 3H, C8–CH3), 2.85, 3.25 (q, dd, J¼3.0,
6.0, 8.0 Hz, 2H, CH2), 4.49 (m, 1H, CHCH3), 7.05 (dd,
J¼7.0, 3.0 Hz, 1H, C7–H), 7.43 (s, 1H, C9–H), 8.20 (s,
1H, C2–H), 8.96 (d, J¼7.0 Hz, 1H, C6–H). Anal. Calcd
for C12H13ClN2O: C, 60.89; H, 5.54; N, 11.83. Found: C,
61.11; H, 5.57; N, 11.90.
1530, 1440 cmꢁ1
.
1H NMR (DMSO-d6): d 1.45 (d, J¼
7.0 Hz, 3H, CH3), 2.41, 3.15 (qd, dq, J¼2.1, 5.9, 7.5 Hz,
2H, CH2), 2.82 (s, 3H, OCH3), 4.70 (m, 1H, CH–Me),
7.05 (d, J¼3.0 Hz, 1H, C7–H), 7.35 (d, J¼8.0 Hz, 1H, C4–
H), 7.55 (d, J¼8.0 Hz, 1H, C5–H), 8.05 (d, J¼12.0 Hz,
1H, ]CH), 10.85 (d, J¼12.0 Hz, 1H, NH). Anal. Calcd
for C14H14N2O3S: C, 57.92; H, 4.86; N, 9.65. Found: C,
57.82; H, 4.71; N, 9.58.
4.5.14. 3-(2-Chloropropyl)-6-methyl-pyrido[1,2-a]pyri-
midin-4(1H)-one (5f). Recrystallized from petroleum ether
as colorless needles: mp 92–93 ꢀC; IR (KBr): 3030, 2990,
1670, 1640, 1590, 1480, 1450, 1430 cmꢁ1
;
1H NMR
4.5.19. 2-[1-(2-Oxo-2,3,4,5-tetrahydrofuran-3-yl)-ethen-
2-yl-amino]-1,3-benzoxazole (7e). Recrystallized from ace-
tonitrile as colorless needles: mp 253–254 ꢀC; IR (KBr):
(CDCl3): d 1.55 (d, J¼7.0 Hz, 3H, CH3), 2.85, 3.05 (q,
dd, J¼3.0, 6.0, 8.0 Hz, 2H, CH2), 3.05 (s, 3H, C6–
CH3), 4.47 (m, 1H, CHMe), 6.65 (m, 1H, C7–H), 7.40
(dd, J¼8.0, 2.9 Hz, 1H, C8–H), 7.65 (d, J¼7.0 Hz, 1H,
C9–H), 8.05 (s, 1H, C2–H). Anal. Calcd for C12H13ClN2O:
C, 60.89; H, 5.54; N, 11.83. Found: C, 61.17; H, 5.24; N,
11.77.
1
3220, 1730, 1650, 1630, 1580, 1530, 1440 cmꢁ1. H NMR
(DMSO-d6): d 3.02 (dt, J¼7.0, 3.0 Hz, 2H, CH2), 4.43 (t,
J¼7.0 Hz, 2H, CH2), 7.21–7.35 (m, 2H, C4–H, C5–H), 7.52
(dd, J¼8.0, 2.5 Hz, 1H, C6–H), 7.63 (dd, J¼8.0, 2.5 Hz,
1H, C7–H), 7.79 (dt, J¼12.0, 3.0 Hz, 1H, ]CH), 10.9 (br s,
1H, NH). Anal. Calcd for C12H10N2O3: C, 62.61; H, 4.38; N,
12.17. Found: C, 62.52; H, 4.38; N, 12.15.
4.5.15. 2-[1-(2-Oxo-2,3,4,5-tetrahydrofuran-3-yl)-ethen-
2-yl-amino]-1,3-benzothiazole (7a). Recrystallized from
N,N-dimethylformamide as pale yellow needles: mp 249–
2350 ꢀC; IR (KBr): 3260, 1720, 1670, 1630, 1600, 1530,
4.5.20. 2-[1-(5-Methyl-2-oxo-2,3,4,5-tetrahydrofuran-
3-yl)-ethen-2-yl-amino]-1,3-benzoxazole (7f). Recrystal-
lized from methanol as colorless needles: mp 160–161 ꢀC;
IR (KBr): 3260, 3060, 1710, 1640, 1580, 1500,
1
1440 cmꢁ1. H NMR (DMSO-d6): d 2.95 (dt, J¼7.0, 3 Hz,
2H, CH2), 4.43 (t, J¼7.0 Hz, 2H, CH2Cl), 7.15 (dt, J¼8.0,
2.0 Hz, 1H, C7–H), 7.25 (dt, J¼8.0, 2.0 Hz, 1H, C4–H),
7.75 (dd, J¼8.0, 2.0 Hz, 1H, C5–H), 7.90 (dd, J¼8.0,
2.0 Hz, 1H, C6), 8.02 (dt, J¼12.0, 3.0 Hz, 1H, ]CH),
11.05 (d, J¼12.0 Hz, 1H, NH). 13C NMR (DMSO-d6):
d 25.2, 67.0, 104.1, 121.7, 123.3, 124.8, 129.0, 132.9,
133.7, 152.6, 163.3, 174.2. Anal. Calcd for C12H10N2O2S:
C, 58.52; H, 4.09; N, 11.37; S, 13.02. Found: C, 58.87; H,
3.92; N, 11.44; S, 13.20.
1
1460 cmꢁ1. H NMR (DMSO-d6): d 1.45 (d, J¼7 Hz, 3H,
CH3), 2.55, 3.24 (qd, dq, J¼2.1, 5.9, 7.5 Hz, 2H, CH2),
4.75 (m, 1H, CHMe), 7.23 (dd, J¼8.0, 2.0 Hz, 1H, C7–H),
7.25–7.35 (m, 2H, C4 & C6–H), 7.45 (dd, J¼8.0, 2.0 Hz,
1H, C6–H), 7.53 (dt, J¼12.0, 3.0 Hz, 1H, ]CH), 9.92 (d,
J¼12.0 Hz, 1H, NH). Anal. Calcd for C13H12N2O3: C,
63.93; H, 4.95; N, 11.47. Found: C, 63.95; H, 4.89; N, 11.55.
4.5.21. 3-[2-(2-Thiazoloamino)-methylidene]-4,5-dihy-
drofuran-2(3H)-one (7g). Recrystallized from ethanol as
colorless needles: mp 213–214 ꢀC; IR (KBr): 3380, 1720,
4.5.16. 2-[1-(5-Methyl-2-oxo-2,3,4,5-tetrahydrofuran-3-
yl)-ethen-2-yl-amino]-1,3-benzothiazole (7b). Recrystal-
lized from methanol as colorless needles: mp 200–201 ꢀC;
IR (KBr): 3200, 3040, 1720, 1670, 1640, 1600, 1540,
1670, 1630, 1520, 1470 cmꢁ1 1H NMR (DMSO-d6):
.
d 2.95 (dt, J¼7.0, 3.0 Hz, 2H, CH2), 4.45 (t, J¼7.0 Hz,

8162
R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
2H, CH2O), 7.12 (d, J¼8.0 Hz, 1H, C4–H), 7.35 (d, J¼
8.0 Hz, 1H, C5–H), 7.85 (dt, J¼12.0, 3.0 Hz, 1H, ]CH),
10.56 (d, J¼12.5 Hz, 1H, NH). Anal. Calcd for
C8H8N2O2S: C, 48.97; H, 4.11; N, 14.28. Found: C, 49.17;
H, 3.91; N, 14.15.
colorless needles: mp 141–143 ꢀC; IR (KBr): 1660, 1600,
1510, 1470, 1440 cmꢁ1 1H NMR (CDCl3): d 3.02 (t,
J¼7.0 Hz, 2H, CH2), 3.95 (t, J¼7.0 Hz, 2H, CH2Cl), 7.30–
8.25 (m, 4H, Ar–H), 7.95 (s, 1H, C2–H). Anal. Calcd for
C12H9ClN2O2: C, 57.96; H, 3.65; N, 11.27. Found: C,
58.12; H, 3.35; N, 11.3.
.
4.5.22. 3-[2-(2-Thiazoloamino)-methylidene]-5-methyl-
4,5-dihydrofuran-2(3H)-one (7h). Recrystallized from ace-
tone/ligroin (1:2) as colorless needles: mp 168 ꢀC; IR (KBr):
4.5.28. 3-(2-Chloropropyl)-1,3-benzoxazolo[3,2-a]pyr-
imidin-4(1H)-one (8f). Recrystallized from ligroin as pale
yellow needles: mp 130–131 ꢀC; IR (KBr): 1680, 1600,
1
3280, 3040, 1720, 1660, 1640, 1520, 1470, 1440 cmꢁ1. H
1
NMR (DMSO-d6): d 1.32 (d, J¼8.0 Hz, 3H, CH3), 4.56 (m,
1H, –CHMe), 2.35, 3.15 (dq, qd, J¼2.1, 5.9, 7.5 Hz, 2H,
CH2), 6.72 (d, J¼8.0 Hz, 1H, C4–H), 7.23 (d, J¼8.0 Hz,
1H, C5–H), 7.82 (dt, J¼12.0, 3.0 Hz, 1H, ]CH), 9.72 (br
s, 1H, NH). Anal. Calcd for C9H10N2O2S: C, 51.41; H,
4.76; N, 13.32. Found: C, 51.67; H, 4.77; N, 13.44.
1520, 1450 cmꢁ1; H NMR (CDCl3): d 1.55 (d, J¼8.0 Hz,
3H, CH3), 2.80 (q, dd, J¼3.0, 6.0, 8.0 Hz, 2H, CH2), 4.71
(m, 1H, –CHMe), 7.30–78.25 (m, 4H, Ar–H), 7.95 (s, 1H,
C2–H). Anal. Calcd for C13H11ClN2O2: C, 59.44; H, 4.22;
N, 10.66. Found: C, 59.21; H, 4.23; N, 10.62.
4.5.29. 6-(2-Chloroethyl)-1,3-thiazolo[2,3-b]pyrimidin-
5(1H)-one (8g). Recrystallized from cyclohexane as pale
yellow needles: mp 86–87 ꢀC; IR (KBr): 1670, 1560,
4.5.23. 3-(2-Chloroethyl)-1,3-benzothiazolo[3,2-a]-
pyrimidin-4(1H)-one (8a). Recrystallized from ethanol as
pale yellow needles: mp 190–191 ꢀC; IR (KBr): 1670,
1500, 1450, 1420 cmꢁ1 1H NMR (CDCl3): d 3.03 (t,
.
1630, 1580, 1500, 1450 cmꢁ1
.
1H NMR (DMSO-d6):
J¼7.0 Hz, 2H, –CH2), 3.85 (t, J¼7.0 Hz, 2H, CH2Cl), 7.05
(d, J¼8.0 Hz, 1H, C4–H), 8.02 (s, 1H, ]C–H), 8.03
(d, J¼8.0 Hz, 1H, C5–H). Anal. Calcd for C8H7ClN2O2S:
C, 44.76; H, 3.29; N, 13.05. Found: C, 44.83; H, 3.11; N,
13.17.
d 3.02 (t, J¼7.0 Hz, 2H, CH2), 3.95 (t, J¼7.0 Hz, 2H,
CH2O), 7.55–7.65 (m, 2H, C8–H, C9–H), 8.02 (dt, J¼8.0,
2 Hz, 1H, C6–H), 9.02 (dt, J¼8.0, 2 Hz, 1H, C7–H), 8.12
(s, 1H, C2H). Anal. Calcd for C12H9ClN2OS: C, 54.44; H,
3.43; N, 10.58, Cl, 13.39. Found: C, 54.54; H, 3.29; N,
10.61, Cl, 13.45.
4.5.30. 3-(2-Hydroxyethyl)-1,3-benzimidazolo[3,2-a]pyr-
imidin-4(1H)-one (11a). Recrystallized from acetonitrile
as colorless needles: mp 203–204 ꢀC; yield 70% (Method
A), yield 68% (Method B); IR (KBr): 3350, 2900, 1740,
4.5.24. 3-(2-Chloropropyl)-1,3-benzothiazolo[3,2-a]pyr-
imidin-4(1H)-one (8b). Recrystallized from ligroin as pale
yellow needles: mp 100–101 ꢀC; IR (KBr): 1670, 1590,
1670, 1610, 1570, 1500, 1490, 1420 cmꢁ1 1H NMR
.
1500, 1450 cmꢁ1
.
1H NMR (DMSO-d6): d 1.55 (d,
(DMSO-d6): d 2.85 (t, J¼7.0 Hz, 2H, CH2), 4.32 (t,
J¼7.0 Hz, 2H, CH2), 7.32–7.56 (m, 3H, Ar–H), 7.95 (s,
1H, C2–H), 8.42 (d, J¼8.0 Hz, 1H, C9–H), 12.6 (br s, 1H,
NH). Anal. Calcd for C12H11N3O2: C, 62.87; H, 4.84; N,
18.33. Found: C, 62.63; H, 4.86; N, 18.19.
J¼8.0 Hz, 3H, CH3), 2.80 (qd, dq, 2H, J¼3.0, 6.0, 8.0 Hz,
CH2), 4.71 (m, 1H, CHMe), 7.55–7.65 (m, 2H, C8–H, C9–
H), 7.89 (s, 1H, C3H), 8.04 (dt, J¼8.0, 2.0 Hz, 1H, C6–H),
9.02 (dt, J¼8.0, 2.0 Hz, 1H, C7–H). Anal. Calcd for
C13H11ClN2OS: C, 56.01; H, 3.98; N, 10.05; Cl, 12.72.
Found: C, 56.11; H, 3.93; N, 10.06; Cl, 13.01.
4.5.31. 3-(2-Hydroxypropyl)-1,3-benzimidazolo[3,2-
a]pyrimidin-4(1H)-one (11b). Recrystallized from metha-
nol as colorless needles: mp 190–191 ꢀC; yield 69%
(Method A), yield 65% (Method B); IR (KBr): 3350,
4.5.25. 3-(2-Chloroethyl)-8-methoxy-1,3-benzothi-
azolo[3,2-a]pyrimidin-4(1H)-one (8c). Recrystallized from
methanol as pale yellow needles: mp 156–157 ꢀC; IR
(KBr): 1660, 1630, 1600, 1570, 1520, 1480, 1440 cmꢁ1. 1H
NMR (DMSO-d6): d 3.02 (t, J¼7.0 Hz, 2H, CH2), 3.095 (t,
J¼7.0 Hz, 2H, CH2), 3.92 (s, 3H, OCH3), 7.15 (dt, J¼8.0,
3.0 Hz, 1H, C7–H), 7.72 (d, J¼3.0 Hz Hz, 1H, C9–H), 7.91
(s, 1H, C2–H), 8.85 (d, J¼8.0 Hz, 1H, C6–H). Anal. Calcd
for C13H11ClN2O2S: C, 52.97; H, 3.76; N, 9.50. Found: C,
52.81; H, 3.83; N, 9.60.
1
3150, 2900, 1670, 1630, 1580, 1500, 1450 cmꢁ1. H NMR
(DMSO-d6): d 1.42 (d, J¼7.0 Hz, 3H, CH3), 2.55 (q, dd,
J¼3.0, 6.0, 8.0 Hz, 2H, CH2), 4.45 (m, 1H, CHMe), 7.32–
7.56 (m, 3H, Ar–H), 7.95 (s, 1H, C2–H), 8.41 (d,
J¼8.0 Hz, 1H, C9–H), 12.60 (br s, 1H, NH). Anal. Calcd
for C13H13N3O2: C, 64.19; H, 5.39; N, 17.27. Found: C,
64.06; H, 5.51; N, 17.26.
4.5.32. 3-(2-Chloroethyl)-4-chloro-1,3-benzimid-
azolo[3,2-a]pyrimidine(12a).A mixture of 12a (0.01 mol)
and phosphorous oxychloride (30 mL) was refluxed for
3 h. The solvent was evaporated in vacuum and the remain-
ing solid was stirred with water (50 mL) for 30 min, neutral-
ized with sodium carbonate (6 g), stirred further for 5 h,
filtered, dried, and recrystallized from ethanol as colorless
needles: mp 220–221 ꢀC; yield 62%; IR (KBr): 2980, 1640,
1600, 1520, 1480, 1450, 1410 cmꢁ1. 1H NMR (DMSO-d6):
d 3.52 (t, J¼7.0 Hz, 2H, CH2), 4.03 (t, J¼7.0 Hz, 2H,
CH2Cl), 7.42–7.72 (m, 2H, C7–H, C8–H), 7.88 (d, J¼
8.0 Hz, 1H, C6–H), 8.35 (d, J¼8.0 Hz, 1H, C9–H), 9.65 (s,
1H, C2–H). Anal. Calcd for C12H9Cl2N3: C, 54.16; H,
3.41; N, 15.79. Found: C, 54.20; H, 3.47; N, 15.77.
4.5.26. 3-(2-Chloropropyl)-8-methoxy-1,3-benzothi-
azolo[3,2-a]pyrimidin-4(1H)-one (8d). Recrystallized from
ligroin as pale yellow needles: mp 141–142 ꢀC; IR (KBr):
1
1660, 1600, 1510, 1470, 1440 cmꢁ1. H NMR (DMSO-d6):
d 1.5 (d, J¼8.0 Hz, 3H, CH3), 2.85, 3.15 (q, dd, J¼3.0, 6.0,
8.0 Hz, 2H, CH2), 3.92 (s, 3H, OCH3), 4.72 (m, 1H,
CHMe), 7.05 (dt, J¼8.0, 3.0 Hz, 1H, C7–H), 7.15 (d,
J¼3.0 Hz, 1H, C9–H), 7.90 (s, 1H, C2–H), 9.80 (d,
J¼8.0 Hz, 1H, C6–H). Anal. Calcd for C14H13ClN2O2S: C,
54.46; H, 4.24; N, 9.07. Found: C, 54.15; H, 4.05; N, 8.95.
4.5.27. 3-(2-Chloroethyl)-1,3-benzoxazolo[3,2-a]pyrim-
idin-4(1H)-one (8e). Recrystallized from ligroin as

R. B. Toche et al. / Tetrahedron 63 (2007) 8157–8163
8163
7. Bruno, O.; Brullo, C.; Schenone, S.; Bondavalli, F.; Ranise, A.;
Tognolini, M.; Impicciatore, M.; Ballabeni, V.; Barocelli, E.
Bioorg. Med. Chem. 2006, 14, 121.
8. Toche, R.; Jachak, M.; Medhane, V.; Desai, A. J. Indian Chem.
Soc. 2006, 83, 1.
Acknowledgements
Authors thank UGC, New Delhi for financial support under
MRP. We also thank Professor Thomas Kappe, Department
of Organic and Bio-organic Chemistry, University of Graz,
Austria for encouragement and the higher authorities of
NDMVP Samaj and KTHM College, Nashik.
9. Jachak, M.; Avhale, A.; Medhane, V.; Toche, R. J. Heterocycl.
Chem. 2006, 43, 1.
10. Jachak, M.; Tantak, C.; Toche, R.; Badgujar, N. Monatsh.
Chem. 2004, 135, 1529.
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