Synthesis of novel fused 2-aminopyrans and pyranopyrimidones

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Organic Preparations and Procedures
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Synthesis of Novel Fused 2-Aminopyrans
and Pyranopyrimidones
Sandeep R. Patil a , Deepak P. Shelar a , Ramhari V. Rote a
Madhukar N. Jachak a
&
a Department of Chemistry, Organic Chemistry Research Center,
K. R. T. Arts B. H. Commerce and A. M. Science College, Gangapur
Road , Nashik , 422002 , (M. S.) , India
Published online: 24 Oct 2013.
To cite this article: Sandeep R. Patil , Deepak P. Shelar , Ramhari V. Rote & Madhukar N. Jachak
(2013) Synthesis of Novel Fused 2-Aminopyrans and Pyranopyrimidones, Organic Preparations
and Procedures International: The New Journal for Organic Synthesis, 45:6, 483-493, DOI:
10.1080/00304948.2013.834776
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Organic Preparations and Procedures International, 45:483–493, 2013
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2013.834776
Synthesis of Novel Fused 2-Aminopyrans
and Pyranopyrimidones
Sandeep R. Patil, Deepak P. Shelar, Ramhari V. Rote,
and Madhukar N. Jachak
Department of Chemistry, Organic Chemistry Research Center, K. R. T.
Arts B. H. Commerce and A. M. Science College, Gangapur Road,
Nashik 422002, (M. S.), India
Pyrano-fused heterocycles are important as antibacterials,1 antihistamines,2 antimicrobials,3
enzyme substrates,4 and alkaloids.5 Several patents describe the synthesis and technical im-
portance of pyrano-fused derivatives in high technology applications such as liquid crystal
display devices,6 ink-jets,7 photochromic materials,8 and electroluminescent materials.9
Pyrano-fused dyes attract special attention on account of their strong fluorescence.10–13
Wang et al. have prepared 2-aminobenzo[h]chromene and naphtho[1,2-b;6,5-bꢀ]dipyran
derivatives from the reaction of 1-naphthol or 1,5-naphthalenediol with aromatic alde-
hydes, malononitri- le or ethyl cyanoacetate catalyzed by KF-Al2O3 in ethanol.14 Marco
et al. have synthesized asymmetrical 3-alkoxycarbonyl-2-amino-4-aryl-4H-naphthol[1,2-
b]pyrans through the Mich-ael addition of 1-naphthol to arylidenecyanoacetates catalyzed
by piperidine in toluene,15 and similarly Elnagdi, Aal and Yassin have performed the ad-
dition of dimedone to arylidene- malononitriles catalyzed by piperidine in acetic acid to
obtain benzo[b]pyran derivatives.16 We reported previously the synthesis of benzochromene
and benzoquinoline derivatives by the Michael addition of 6-methoxy-1-tetralone to
benzylidenemalononitrile catalyzed by piperidine in ethanol and ammonium acetate in
ethanol respectively.17 However, the development of simpler, environmentally benign, high-
yielding, and clean syntheses of novel pyran derivatives is still in demand. The drive towards
clean technology has also encouraged the application of solvent-free conditions in organic
synthesis. We now report the synthesis of 2-aminopyran derivatives 4 in 78–84% overall
yields from 1 as shown in Scheme 1.
Thus, previously reported18 compounds 1 on treatment with diethyl malonate in toluene
at reflux furnished ethyl-2-(3-aryl-1-phenyl-1H-pyrazol-5-ylcarbamoyl)-acetates (2) which
were cyclized to 3 by heating in diphenyl ether. Alternatively, compounds 3 were ob-
tained by heating compounds 1 with diethyl malonate in diphenyl ether. Then 3 were
Received March 22, 2013; in final form June 28, 2013.
Address correspondence to Madhukar N. Jachak, Organic Chemistry Research Center, Depart-
ment of Chemistry, K. R. T. Arts B. H. Commerce and A. M. Science College, Gangapur Road,
Nashik 422002, (M. S.), India. E-mail: mnjachak@hotmail.com
483

484
Jachak et al.
Scheme 1
transformed to desired 2-aminopyran derivatives 4 by heating with 2-(4-chlorobenzylidene)
malononitrile or (E)-ethyl 3-(4-chlorophenyl)-2-cyanoacrylate or (E)-3-(4-chlorophenyl)-
2-cyanoacrylamide in ammonium acetate at 120◦C.
This conversion of 3 to 4 does not require any solvent and aqueous work-up of
the reaction yielded 4; the acetate ion served as the base in this condensation to give
the products in pure state without further purification. They were characterized by
spectrosco-pic and analytical methods. For example, the infrared spectrum of 4a showed
bands at 3410 cm−1 (amide NH), at 3320 cm−1 and 3241 cm−1 ( NH2), at 2212 cm−1
( CN) and at 1678 cm−1 (CONH). Its mass spectrum exhibited molecular ion peaks
at m/z 525 (M+), 527 (M+2), 529 (M+4) due to the presence of two chlorines. Its
1H-NMR spectrum displayed a singlet at δ 4.55 (1H, for sp3 carbon in pyran ring), a
broad singlet at δ 6.80 (2H, NH2) and a singlet at δ 12.02 (-NH proton of pyridone
ring) in addition to aromatic protons between δ 7.20–8.16. Treatment of 4a,b with
formic acid at reflux for 6 h. yielded the novel 1,6-aryl-3-phenyl-6,10-dihydropyrazolo
[4ꢀꢀ,3ꢀꢀ:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyrimidine-5,7(3H,4H)dion- es (5a,b) in good
yields (67–69%). The amino tetracyclic derivatives 6, e. g. 7-amino-1,6-aryl-4-methyl-3-
phenyl-4,6-dihydropyrazolo[4ꢀꢀ,3ꢀꢀ:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyri-midine-5-(3H)
-one (6a,b) were obtained by condensation of 4a,b with formamide in the presence of
formic acid and dimethylformamide in an analogous manner after 10–11 hrs. (Scheme 2).
Compounds 5 and 6 were characterized by spectroscopic and analytical methods.

Novel Fused 2-Aminopyrans and Pyranopyrimidones
485
Scheme 2
The reaction of 2-amino-4,9-aryl-5-oxo-7-phenyl-4,5,6,7-tetrahydropyrano[2,3-
d]pyrazolo- [3,4-b]pyridine-3-carbonitrile derivatives (4a,b) with triethyl orthoformate
in acetic anhydri- de produced the open-chain derivatives (E)-4,9-aryl-3-cyano-2-
[(ethoxymethylene)amino]-7-phenyl-4,7-dihydropyrano[2,3-d]pyrazolo[3,4-b]pyridin-5-
yl-acetate (7a,b) rather than cycli- zed pyridine derivatives 8 (Scheme 3). Structure 7a
was established based on its infrared spectrum [bands at 2217 cm−1 (CN) and 1715 cm−1
(ester C
O)], its mass spectrum [molecular ion peaks at m/z 623 (M+), 625 (M+2),
627 (M+4)]. In addition to the triplet-quartet signals at δ 1.31 and 4.29 corresponding
1
to the ethyl group, its H-NMR spectrum showed a singlets at δ 2.19 for -CH3, at δ
5.01 for the proton attached to sp3 carbon in pyran ring, at δ 8.04 attributable to the
Scheme 3

486
Jachak et al.
olefinic proton and other aromatic protons between δ 7.30–8.11. Further, the reaction
of 2-amino-4,9-aryl-5-oxo-7-phenyl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyrid
ine-3-carbonitriles (4a,b) with dimethylformamide dimethylacetal (DMF-DMA) furnished
open-chain
derivatives
(E)-Nꢀ-(-4,9-aryl-3-cyano-6-methyl-5-oxo-7-phenyl-4,5,6,7-
amide
tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridin-2-yl)-N,N-dimethylformamid-
(9a,b) in good yields. They were converted into pyrimidine derivatives 10a,b by cycliza-
tion with hydrazine hydrate in DMF (Scheme 3). The analytical and spectroscopic data for
all the new compounds are summarized in Tables 1 and 2.
In conclusion, green approaches have been devised for the preparation of potentially
useful bifunctional pyrano[2,3-d]pyrazolo[3,4-b]pyridine derivatives (4). These methods
inc- lude some important features, such as the solvent-free medium, the use of ammonium
acetate as a green reagent, quantitative yields, and short reaction times. Moreover, the
experimental procedures are very easy to carry out. The enaminonitrile derivatives 4a,b
were utilized for synthesis of substituted new pyrano[2,3-d]pyrazolo[3,4-b]pyridines 7
and 9 and pyrazolo- [4ꢀꢀ,3ꢀꢀ:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyrimidine derivatives 5, 6
and 10.
Table 1
Yield, mps and Elemental Analysis of New Compounds
Cmpd.
Yield (%)
mp. (◦C)
Elemental Analysis (Found)
H
C
N
2a
2b
3a
3b
4a
4b
4c
4d
4e
4f
5a
5b
6a
6b
7a
7b
9a
9b
10a
10b
80
82
86
87
81
84
81
80
79
78
69
67
63
68
76
73
71
72
68
66
124–125
123–124
234–235
238–239
214–242
244–245
238–239
237–238
244–245
241–242
288–289
286–287
287–288
284–285
255–256
258–259
234–235
236–237
269–270
267–268
62.58 (62.34)
56.09 (56.31)
64.01 (64.27)
56.56 (56.33)
63.89 (63.75)
58.91 (58.66)
62.84 (62.58)
58.32 (58.44)
61.78 (61.48)
57.11 (57.33)
62.83 (62.58)
58.16 (58.39)
62.94 (62.68)
58.26 (58.39)
63.93 (63.74)
59.39 (59.10)
64.54 (64.26)
60.06 (59.83)
61.86 (61.51)
57.48 (57.24)
4.73 (4.48)
4.24 (4.03)
3.58 (3.77)
3.16 (3.38)
3.26 (3.44)
3.00 (2.88)
3.87 (3.66)
3.59 (3.87)
3.52 (3.23)
3.25 (3.53)
3.09 (3.28)
2.86 (2.69)
3.28 (3.08)
3.03 (3.30)
3.63 (3.59)
3.38 (3.19)
4.06 (4.22)
3.78 (3.56)
3.63 (3.38)
3.38 (3.07)
10.95 (11.15)
9.81 (9.58)
12.44 (12.30)
10.99 (10.74)
13.30 (13.22)
12.27 (12.54)
9.77 (9.40)
9.07 (8.81)
12.86 (12.97)
11.89 (12.17)
12.63 (12.51)
11.69 (11.48)
15.19 (14.91)
14.06 (14.28)
12.02 (11.74)
11.17 (10.89)
14.11 (13.84)
13.13 (12.87)
16.83 (16.59)
15.64 (15.39)

Novel Fused 2-Aminopyrans and Pyranopyrimidones
487
Table 2
IR, 1H, 13C NMR and Mass Spectra of Compounds.
Cmpd IR
(cm−1
1H NMR (δ)
13C NMR (δ)
Mass Spectra
)
2a
3350, (CDCl3): 1.26 (t, 3H, J = 6.8 Hz, (DMSO-d6): 27.4, 76.5,
383
3015, CH3), 3.46 (s, 2H, CH2), 4.15 (q, 83.6, 112.3, 120.2 (2 Cꢀs),
[M+, 100],
1731, 2H, J = 6.8 Hz, -OCH2), 7.07 (s, 123.1, 126.3, 128.6 (2 Cꢀs), 385
1676, 1H, Ar-H), 7.30–7.51 (m, 5H,
129.1 (2 Cꢀs), 129.7 (2 Cꢀs), [M+2, 33].
1622. Ar-H), 7.53 (d, J = 8.4 Hz, 2H, 132.1, 133.0 (2 Cꢀs), 140.4,
Ar-H), 7.75 (d, J = 8.4 Hz, 2H, 151.3, 159.7, 162.2.
Ar-H), 9.88 (s, 1H, -NH).
2b
3350, (CDCl3): 1.25 (t, 3H, J = 6.8 Hz, (DMSO-d6): 28.6, 77.0,
428
3015, CH3), 3.44 (s, 2H, CH2), 4.17 (q, 86.1, 110.2, 120.0 (2 Cꢀs),
[M+, 100],
1731, 2H, J = 6.8 Hz, -OCH2), 7.08 (s, 123.3, 127.4, 128.5 (2 Cꢀs), 430
1676, 1H, Ar-H), 7.30–7.52 (m, 5H,
129.3 (2 Cꢀs), 129.9 (2 Cꢀs), [M+2, 98].
1622. Ar-H), 7.54 (d, J = 8.4 Hz, 2H, 131.6, 132.4 (2 Cꢀs), 139.7,
Ar-H), 7.74 (d, J = 8.4 Hz, 2H, 150.4, 157.3, 161.5.
Ar-H), 9.89 (s, 1H, -NH).
3a
3b
4a
3419, (DMSO-d6): 6.04 (s, 1H, Ar-H), (DMSO-d6): 90.1, 101.5,
337
3312, 7.30–7.56 (m, 5H, Ar-H), 8.09 (d, 121.2 (2 Cꢀs), 125.7, 128.3 [M+, 100],
1681, J = 8.6 Hz, 2H, Ar-H), 8.26 (d, J (2 Cꢀs), 128.9 (2 Cꢀs), 130.4 339
1619. = 8.6 Hz, 2H, Ar-H), 11.09 (s,
(2Cꢀs), 131.7, 133.0, 139.2, [M+2, 33].
1H, -NH), 11.69 (s, 1H, OH).
143.3, 152.2, 161.4, 165.5
3419, (DMSO-d6): 6.06 (s, 1H, Ar-H), (DMSO-d6): 89.3, 100.5,
382
3312, 7.29–7.54 (m, 5H, Ar-H), 8.07 (d, 120.4 (2 Cꢀs), 123.6, 127.3 [M+, 100],
1681, J = 8.4 Hz, 2H, Ar-H), 8.25 (d, J (2 Cꢀs), 128.2 (2 Cꢀs), 129.8 384
1619. = 8.4 Hz, 2H, Ar-H), 11.08 (s,
(2 Cꢀs), 130.2, 132.4, 137.1, [M+2, 98].
1H, -NH), 11.67 (s, 1H, -OH).
140.6, 150.3, 160.0, 163.6.
3410, (DMSO-d6): 4.55 (s, 1H,
3320, pyran-H), 6.80 (s, 2H, -NH2),
(DMSO-d6): 41.2, 61.6,
525
90.2, 104.1, 117.3, 120.2 (2 [M+, 100],
3241, 7.20 (d, J = 8.4 Hz, 2H, Ar-H), Cꢀs), 125.7, 128.3 (2 Cꢀs),
527
2212, 7.31–7.69 (m, 5H, Ar-H), 7.62 (d, 128.8 (2Cꢀs), 128.9 (2 Cꢀs), [M+2, 65],
1678, J = 8.4 Hz, 2H, Ar-H), 7.96 (d, J 130.4 (2 Cꢀs), 130.5 (2Cꢀs), 529
1632. = 8.6 Hz, 2H, Ar-H), 8.16 (d, J = 131.3, 131.7, 133.0, 139.2, [M+4, 11].
8.6 Hz, 2H, Ar-H), 12.02 (s, 1H, 140.3, 143.3, 152.2, 158.2,
-NH).
162.5, 164.4.
4b
3410, (DMSO-d6): 4.54 (s, 1H,
(DMSO-d6): 39.7, 60.3,
570
3320, pyran-H), 6.80 (s, -NH2), 7.21 (d, 91.2, 102.5, 116.3, 120.2 (2 [M+, 100],
3241, J = 8.4 Hz, 2H, Ar-H), 7.30–7.69 Cꢀs), 124.7, 128.2 (2 Cꢀs),
572
2212, (m, 5H, Ar-H), 7.64 (d, J =
128.6 (2Cꢀs), 128.8 (2 Cꢀs), [M+2, 82],
1678, 8.4 Hz, 2H, Ar-H), 7.97 (d, J = 131.3 (2 Cꢀs), 131.6 (2Cꢀs), 574
1632. 8.6 Hz, 2H, Ar-H), 8.16 (d, J = 131.9, 132.0, 132.8, 137.3, [M+4, 32].
8.6 Hz, 2H, Ar-H), 12.01 (s, 1H, 139.6, 141.3, 151.2, 156.6,
-NH).
161.1, 162.6.
(Continued on next page)

488
Jachak et al.
Table 2
IR, 1H, 13C NMR and Mass Spectra of Compounds (Continued).
Cmpd IR
1H NMR (δ)
13C NMR (δ)
Mass Spectra
(cm−1
)
4c
3435, (DMSO-d6): 1.16 (t, 3H, J =
3387, 6.5 Hz, CH3), 4.10 (q, 2H, J =
3259, 6.5 Hz, -OCH2), 4.97 (s, 1H,
1732, pyran-H), 7.22 (d, J = 8.4 Hz,
1681, 2H, Ar-H), 7.31–7.69 (m, 5H,
(DMSO-d6): 14.2, 41.2,
61.6, 90.1, 104.0, 105.1,
572
[M+, 100],
120.2 (2 Cꢀs), 125.7, 128.3 574
(2 Cꢀs), 128.8 (2 Cꢀs), 128.9 [M+
(2 Cꢀs), 130.4 (2 Cꢀs), 130.5 2,65], 576
1630. Ar-H), 7.63 (d, J = 8.4 Hz, 2H, (2 Cꢀs), 131.2, 131.7, 133.0, [M+
Ar-H), 8.03 (d, J = 8.6 Hz, 2H, 139.2, 140.3, 143.3, 152.2, 4,11].
Ar-H), 8.12 (d, J = 8.6 Hz, 2H, 158.2, 161.0, 162.4, 167.7.
Ar-H), 12.02 (s, 1H, -NH).
4d
3435, (DMSO-d6): 1.15 (t, 3H, J =
3387, 6.5 Hz, CH3), 4.11 (q, 2H, J =
3259, 6.5 Hz, -OCH2), 4.97 (s, 1H,
1732, pyran-H), 7.24 (d, J = 8.4 Hz,
1681, 2H, Ar-H), 7.30–7.68 (m, 5H,
(DMSO-d6): 18.3, 40.5,
60.2, 89.4, 102.3, 103.4,
617
[M+, 100],
120.6 (2 Cꢀs), 124.2, 128.1 619
(2 Cꢀs), 128.6 (2 Cꢀs), 128.8 [M+
(2 Cꢀs), 130.0 (2 Cꢀs), 130.3 2,80],
1630. Ar-H), 7.67 (d, J = 8.4 Hz, 2H, (2 Cꢀs), 130.6, 131.1, 132.3, 621
Ar-H), 8.06 (d, J = 8.6 Hz, 2H, 137.6, 139.3, 140.3, 151.4, [M+
Ar-H), 8.14 (d, J = 8.6 Hz, 2H, 156.3, 160.2, 162.0, 166.2. 4,32].
Ar-H), 12.01 (s, 1H, -NH).
4e
4f
3465, (DMSO-d6): 4.53 (s, 1H,
(DMSO-d6): 41.1, 90.1, 104. 543
3378, pyran-H), 6.80 (s, 2H, -NH2),
6, 105.2, 120.2 (2 Cꢀs), 125 [M+, 100],
3352, 7.20 (d, J = 8.4 Hz, 2H, Ar-H), .7, 128.3 (2 Cꢀs), 128.8 (2
545
3268, 7.30–7.69 (m, 5H, Ar-H), 7.63 (d, Cꢀs), 128.9 (2 Cꢀs), 130.4 (2 [M+
3247, J = 8.4 Hz, 2H, Ar-H), 7.69 (s,
Cꢀs), 130.5 (2 Cꢀs), 131.2,
2,65], 547
1683, 2H, -NH2), 7.97 (d, J = 8.6 Hz, 131.7, 133.0, 139.2, 140.3, [M+
1676, 2H, Ar-H), 8.17 (d, J = 8.6 Hz, 143.3, 152.2, 158.2, 161.0, 4, 11].
1618. 2H, Ar-H), 12.01 (s, 1H, -NH).
3465, (DMSO-d6): 4.54 (s, 1H,
161.7, 171.2.
(DMSO-d6): 40.4, 90.0, 103. 588
3378, pyran-H), 6.82 (s, 2H, -NH2),
2, 104.5, 120.6 (2 Cꢀs), 123. [M+, 100],
3352, 7.22 (d, J = 8.4 Hz, 2H, Ar-H), 2, 128.0 (2 Cꢀs), 128.4 (2
590
3268, 7.30–7.69 (m, 5H, Ar-H), 7.66 (d, Cꢀs), 128.7 (2 Cꢀs), 130.0 (2 [M+
3247, J = 8.4 Hz, 2H, Ar-H), 7.69 (s,
Cꢀs), 130.3 (2 Cꢀs), 131.4,
2,82], 592
1683, 2H, -NH2), 7.99 (d, J = 8.6 Hz, 131.9, 133.2, 137.6, 139.3, [M+
1676, 2H, Ar-H), 8.16 (d, J = 8.6 Hz, 141.4, 150.6, 156.6, 160.2, 4,32].
1618. 2H, Ar-H), 12.02 (s, 1H, -NH).
3468, (DMSO-d6): 4.55 (s, 1H,
3368, pyran-H), 5.10 (s, 1H,
1677, pyrimidine-H), 7.20–8.20 (m,
1669, 13H, Ar-H), 8.51 (s, 1H,
1630. pyrimidine-NH), 12.02 (s, 1H,
pyridine-NH).
160.7, 169.5.
5a
(DMSO-d6): 41.3, 90.1,
553
91.8, 105.2, 120.2 (2 Cꢀs),
[M+, 100],
125.7, 128.3 (2 Cꢀs), 128.8 555
(2 Cꢀs), 128.9 (2 Cꢀs), 130.4 [M+
(2 Cꢀs), 130.5 (2 Cꢀs), 131.2, 2,65], 557
131.7, 133.0, 139.2, 140.3, [M+
143.3, 150.2, 152.2, 158.2, 4,11].
161.1, 169.4, 176.9.
(Continued on next page)

Novel Fused 2-Aminopyrans and Pyranopyrimidones
489
Table 2
IR, 1H, 13C NMR and Mass Spectra of Compounds (Continued).
Cmpd IR
(cm−1
1H NMR (δ)
13C NMR (δ)
Mass Spectra
)
5b
6a
6b
7a
3468, (DMSO-d6): 4.55 (s, 1H,
3368, pyran-H), 5.10 (s, 1H,
1677, pyrimidine-H), 7.20–8.20 (m,
1669, 13H, Ar-H), 8.46 (s, 1H,
1630. pyrimidine-NH), 12.02 (s, 1H,
pyridine-NH).
(DMSO-d6): 40.2, 90.0,
598
91.2, 103.2, 120.4 (2 Cꢀs),
[M+, 100],
123.9, 128.0 (2 Cꢀs), 128.4 600
(2 Cꢀs), 128.7 (2 Cꢀs), 129.2 [M+2, 65],
(2 Cꢀs), 129.6 (2 Cꢀs), 130.3, 602
130.7, 132.0, 137.3, 139.6, [M+4, 32].
141.3, 149.0, 150.4, 156.3,
159.5, 164.7, 171.3.
3412, (DMSO-d6): 4.67 (s, 1H,
3328, pyran-H), 6.20 (s, 1H,
(DMSO-d6): 41.2, 90.1, 106 552
.8, 112.2, 120.2 (2 Cꢀs), 125 [M+, 100],
1678, pyrimidine-H), 7.29–8.26 (m,
.7, 128.3 (2 Cꢀs), 128.8 (2
554
1622. 13H, Ar-H), 8.91 (s, 2H, -NH2), Cꢀs), 128.9 (2 Cꢀs), 130.4 (2 [M+2, 65],
12.01 (s, 1H, -NH).
Cꢀs), 130.5 (2 Cꢀs), 131.2,
556
131.7, 133.0, 139.3, 140.3, [M+4, 11].
143.3, 145.8, 152.1, 158.3,
161.0, 162.1, 174.4.
3412, (DMSO-d6): 4.66 (s, 1H,
3328, pyran-H), 6.24 (s, 1H,
(DMSO-d6): 40.4, 90.0, 104 597
.9, 111.3, 120.0 (2 Cꢀs), 123 [M+, 100],
1678, pyrimidine-H), 7.28–8.27 (m,
.3, 128.0 (2 Cꢀs), 128.6 (2
599
1622. 13H, Ar-H), 8.94 (s, 2H, -NH2), Cꢀs), 128.9 (2 Cꢀs), 130.0 (2 [M+2, 78],
12.01 (s, 1H, -NH).
Cꢀs), 130.3 (2 Cꢀs), 131.0,
131.4, 132.7, 137.2, 139.1, [M+4, 32].
141.2, 143.7, 151.3, 154.3,
160.0, 161.3, 171.2.
602
3012, (DMSO-d6): 1.31 (t, 3H, J =
(DMSO-d6): 17.1, 20.8,
623
2971, 7.5 Hz, CH3), 2.19 (s, 3H, CH3), 41.2, 63.3, 77.9, 81.1, 90.1, [M+, 100],
2217, 4.29 (q, 2H, J = 7.5 Hz, -OCH2), 105.0, 117.3, 120.2 (2 Cꢀs), 625
1715, 5.01 (s, 1H, pyran-H), 7.39–7.47 125.7, 128.3 (2 Cꢀs), 128.8 [M+2, 65],
1621. (m, 5H, Ar-H),7.58 (d, J =
(2 Cꢀs), 128.9 (2 Cꢀs), 130.4 627
8.4 Hz, 2H, Ar-H), 7.63 (d, J = (2 Cꢀs), 130.5 (2 Cꢀs), 131.2, [M+4, 11].
8.4 Hz, 2H, Ar-H), 8.04 (s, 1H), 131.6, 133.0, 139.3, 140.3,
8.06 (d, J = 8.6 Hz, 2H, Ar-H), 143.4, 152.2, 155.6, 158.3,
8.11 (d, J = 8.6 Hz, 2H, Ar-H). 169.8, 170.3.
7b
3012, (DMSO-d6): 1.30 (t, 3H, J =
(DMSO-d6): 17.3, 21.5,
668
2971, 6.8 Hz, CH3), 2.17 (s, 3H, CH3), 40.3, 61.7, 76.3, 80.4, 90.6, [M+, 100],
2217, 4.30 (q, 2H, J = 6.8 Hz, -OCH2), 103.3, 117.0, 120.0 (2 Cꢀs), 670
1715, 4.91 (s, 1H, pyran-H), 7.39–7.49 123.6, 128.0 (2 Cꢀs), 128.6 [M+2, 68],
1621. (m, 5H, Ar-H), 7.56 (d, J =
(2 Cꢀs), 128.9 (2 Cꢀs), 129.9 672
8.4 Hz, 2H, Ar-H), 7.64 (d, J = (2 Cꢀs), 130.3 (2 Cꢀs), 131.0, [M+4, 32].
8.4 Hz, 2H, Ar-H), 8.06 (s, 1H), 131.6, 132.7, 137.6, 139.1,
8.08 (d, J = 8.6 Hz, 2H, Ar-H), 140.3, 150.2, 154.6, 156.0,
8.12 (d, J = 8.6 Hz, 2H, Ar-H). 168.3, 169.7.
(Continued on next page)

490
Jachak et al.
Table 2
IR, 1H, 13C NMR and Mass Spectra of Compounds (Continued).
Cmpd IR
1H NMR (δ)
13C NMR (δ)
Mass Spectra
594
(cm−1
)
9a
3011, (DMSO-d6): 3.02 (s, 6H, -2CH3), (DMSO-d6): 30.8, 40.0 (2
2232, 3.90 (s, 3H, N-CH3), 4.72 (s, 1H, Cꢀs), 41.2, 77.9, 90.2, 105.1, [M+, 100],
1377, pyran-H), 7.31–8.01 (m, 10H,
117.3, 120.2 (2 Cꢀs), 125.7, 596
1617. Ar-H+olefinic-H), 8.05 (d, J = 128.3 (2 Cꢀs), 128.8 (2 Cꢀs), [M+2, 65],
8.6 Hz, 2H, Ar-H), 8.22 (d, J = 128.9 (2 Cꢀs), 130.4 (2 Cꢀs), 598
8.6 Hz, 2H, Ar-H).
130.5 (2 Cꢀs), 131.2, 131.7, [M+4, 11].
133.0, 139.3, 140.3, 143.3,
152.2, 156.2, 157.3, 162.5,
170.3.
9b
3011, (DMSO-d6): 3.04 (s, 6H, -2CH3), (DMSO-d6): 31.4, 40.6 (2
639
114.6, 120.1 (2 Cꢀs), 124.3, 641
2232, 3.91 (s, 3H, N-CH3), 4.74 (s, 1H, Cꢀs), 41.6, 78.0, 90.4, 103.7, [M+, 100],
1377, pyran-H), 7.31–8.06 (m, 10H,
1617. Ar-H+olefinic-H), 8.10 (d, J = 128.1 (2 Cꢀs), 128.4 (2 Cꢀs), [M+2, 90],
8.6 Hz, 2H, Ar-H), 8.24 (d, J = 128.8 (2 Cꢀs), 130.0 (2 Cꢀs), 643
8.6 Hz, 2H, Ar-H).
130.3 (2 Cꢀs), 131.1, 131.6, [M+4, 32].
133.2, 137.6, 139.7, 142.3,
150.6, 157.0, 157.9, 161.3,
168.7.
10a 3381, (DMSO-d6): 3.90 (s, 3H, N-CH3), (DMSO-d6): 30.8, 41.2,
581
3306, 4.72 (s, 1H, pyran-H), 5.96 (s, 2H, 90.1, 93.0, 105.3, 120.2 (2 [M+, 100],
3205, NH2), 6.22 (s, 1H, pyrimidine-H), Cꢀs), 125.7, 128.3 (2 Cꢀs),
583
1647, 7.31–8.01 (m, 10H, Ar-H+NH), 128.8 (2 Cꢀs), 128.9 (2 Cꢀs), [M+2, 66],
1616, 8.05 (d, J = 8.6 Hz, 2H, Ar-H), 130.4 (2 Cꢀs), 130.5 (2 Cꢀs), 585
1210. 8.22 (d, J = 8.6 Hz, 2H, Ar-H). 131.2, 131.6, 133.2, 139.2, [M+4, 21].
140.3, 143.2, 152.2, 156.0,
156.2, 158.3, 161.0, 164.1.
10b 3380, (DMSO-d6): 3.88 (s, 3H, N-CH3), (DMSO-d6): 31.0, 40.4,
626
3308, 4.74 (s, 1H, pyran-H), 5.93 (s,
3207, 2H, -NH2), 6.20 (s, 1H,
90.6, 92.3, 103.6, 120.0 (2 [M+, 100],
Cꢀs), 123.6, 128.0 (2 Cꢀs),
628
1649, pyrimidine-H),7.31–8.01 (m,
1618, 10H, Ar-H+NH), 8.04 (d, J =
128.6 (2 Cꢀs), 128.8 (2 Cꢀs), [M+2, 92],
129.6 (2 Cꢀs), 130.0 (2 Cꢀs), 630
1215. 8.6 Hz, 2H, Ar-H), 8.21 (d, J = 131.3, 131.9, 132.2, 137.7, [M+4, 18].
8.6 Hz, 2H, Ar-H).
139.2, 140.3, 151.3, 154.1,
156.0, 156.6, 159.3, 161.0.
Experimental Section
Melting points were determined on a Gallenkamp melting point apparatus, Model MFB595
in open capillary tubes and are uncorrected. 1H (300 MHz) and 13C NMR (75 MHz) spectra
were recorded on a Varian XL-300 spectrometer in CDCl3 and DMSO-d6 with TMS as an
internal standard. Chemical shifts are reported in δ form. Infrared spectra were determined

Novel Fused 2-Aminopyrans and Pyranopyrimidones
491
on a Shimadzu FTIR-408 instrument as potassium bromide pellets. Elemental analyses
were performed on a Hosli CH-Analyzer and are within 0.3 of the theoretical percentage.
High-resolution mass spectra were obtained on a Mat 112 Varian Mat Bremen (70 eV) mass
spectrometer. Solutions were concentrated on a rotary evaporator under reduced pressure.
All reactions were monitored by thin layer chromatography (ethylacetate/n-hexane, 4:1),
carried out on 0.2 mm silica gel 60 F254 (Merck) plates using UV light (250 nm and 400 nm)
for detection.
General Procedure for the Synthesis of Ethyl 2-(3-Aryl-1-phenyl-1H-pyrazol-5-
ylcarbamoyl) Acetates (2a,b). A solution of 5-aminopyrazole 1a (2.69 g, 0.01 mol) or
1b (3.14 g, 0.01 mol) and diethyl malonate (1.60 g, 0.01 mol) in toluene (25 ml) containing
a catalytic amount of triethylamine was refluxed for 10–12 h. After completion of reaction
(TLC check), the solvent was removed under reduced pressure to give a colorless solid.
The crude solid was stirred in methanol (10 ml), collected, dried under high vacuum, and
recrystallized from ethanol to give 2a,b.
General Procedure for the Synthesis of 3-Aryl-4-hydroxy-1-phenyl-1H-pyrazolo[3,4-b]
pyridine-6(7H)-ones (3a,b)
A. A solution of 2a (3.83 g, 0.01 mol) or 2b (4.28 g, 0.01 mol) and diphenyl ether (30 ml)
was refluxed for 1 h. After completion of reaction (TLC check), the reaction mixture was
allowed to cool at room temperature. The separated solid was stirred in diethyl ether (50 ml)
for 1 h, collected, washed with diethyl ether, dried and recrystallized from ethanol:DMF
(9:1) to give 3a,b.
B. A solution of 5-aminopyrazole 1a (2.69 g, 0.01 mol) or 1b (3.14 g, 0.01 mol) and
diethyl malonate (1.60 g, 0.01 mol) in diphenyl ether (25 ml) was refluxed for 1 h. After
completion of reaction (TLC check), the reaction mixture was allowed to cool at room
temperature. The separated solid was stirred in diethyl ether (50 ml) for 1 h, collected,
washed with diethyl ether, dried and recrystallized from ethanol:DMF (9:1) to afford
3a,b.
General Procedure for the Synthesis of 2-amino-4,9-Aryl-5-oxo-7-phenyl-4,5,6,7-
tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridines (4a–f). A mixture of 4-hydroxypy-
razolopyridine 3a (3.37 g, 0.01 mol) or 3b (3.82 g, 0.01 mol) and the 2-(4-
chlorobenzylidene)malononitrile (1.88 g, 0.01 mol) or (E)-ethyl 3-(4-chlorophenyl)-2-
cyanoacrylate (2.35 g, 0.01 mol) or (E)-3-(4-chlorophenyl)-2-cyanoacrylamide(2.06 g,
0.01 mol) in ammonium acetate (7.70 g, 0.10 mol) was thoroughly mixed at room tem-
perature and heated for 1–1.5 h. at 120◦C under a short Vigreux column attached to
the flask. After completion of reaction (TLC check), the reaction mixture was cooled to
room temperature and slowly added to cold water (50 ml) to dissolve excess of ammo-
nium acetate and the precipitated product was collected, washed with water, dried to give
4a–f.
General Procedure for the Synthesis of 1,6-Aryl-3-phenyl-6,10-dihydro-
pyrazolo[4ꢀꢀ,3ꢀꢀ-:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyrimidine-5,7(3H,4H)-diones
(5a,b). A mixture of 4a (5.26 g, 0.01 mol) or 4b (6.70 g, 0.01 mol) and formic acid (30 ml)
was refluxed for 6 h. After completion of reaction (TLC check), the reaction mixture was

492
Jachak et al.
allowed to cool at room temperature. The separated colorless solid was collected and
recrystallized from ethanol:DMF (9:1) to give 5a,b.
General Procedure for the Synthesis of 7-Amino-1,6-Aryl-4-methyl-3-phenyl-
4,6-dihydro-pyrazolo[4ꢀꢀ,3ꢀꢀ:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyrimidine-5(3H)-ones
(6a,b). Compound 4a (5.26 g, 0.01 mol) or 4b (6.70 g, 0.01 mol) was added to a mixture
of formamide (10 ml), formic acid (5 ml) and dimethylformamide (15 ml). The reaction
mixture was refluxed for 10–11 h. After completion of reaction (TLC check), the reaction
mixture was allowed to cool at room temperature. The separated colorless solid was
collected and recrystallized from ethanol:DMF (9:1) to afford 6a,b.
General Procedure for the Synthesis of (E)-4,9-Aryl-3-cyano-2-((ethoxy
methylene)amino)-7-phenyl-4,7-dihydropyrano[2,3-d]pyrazolo[3,4-b]pyridin-5-yl-aceta
tes (7a,b). A mixture of 4a (5.26 g, 0.01 mol) or 4b (6.70 g, 0.01 mol) and triethyl
orthoformate (1.48 g, 0.01 mol) in acetic anhydride (30 ml) was refluxed for 2.5 h (TLC
check). The product which precipitated during reflux was collected after cooling. It was
recrystallized from ethanol:DMF (9:1) to afford 7a,b.
General Procedure for the Synthesis of (E)-Nꢀ-4,9-Aryl-3-cyano-6-methyl-5-oxo-
7-phenyl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridin-2-yl)-N,N-dimethylfor-
mamides (9a,b). A mixture of 4a (5.26 g, 0.01 mol) or 4b (6.70 g, 0.01 mol) and DMF-
DMA (1.19 g, 0.01 mol) in 1,4-dioxane (35 ml) was refluxed for 2 h. After completion of
reaction (TLC check), the reaction mixture was allowed to cool at room temperature. The
separated yellow solid was collected and recrystallized from ethanol:DMF (9:1) to give
9a,b.
General Procedure for the Synthesis of 8-Amino-1,6-Aryl-7-imino-4-methyl-3-
phenyl-4,6-dihydropyrazolo[4ꢀꢀ,3ꢀꢀ:5ꢀ,6ꢀ]pyrido[3ꢀ,4ꢀ:5,6]pyrano[2,3-d]pyrimidine-5(3H)-
ones (10a,b). A mixture of 9a (5.94 g, 0.01 mol) or 9b (6.03 g, 0.01 mol) and hydrazine
hydrate (0.50 g, 0.01 mol) in DMF (25 ml) was refluxed for 5 h. After completion of
reaction (TLC check), the reaction mixture was allowed to cool at room temperature. The
separated colorless solid was collected and recrystallized from ethanol:DMF (9:1) to give
10a,b.
Acknowledgments
The authors thank CSIR New Delhi (India) for financial support, Prof. D. D. Dhavale,
Department of Chemistry, University of Pune for the spectral and analytical data, IIT
(Mumbai) for elemental analysis and Principal KTHM College, Nashik (India) for use of
the facilities.
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