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Supporting Information
Uncatalyzed Four Component Synthesis of Pyrazolopyranopyrimidine Derivatives and Their
Antituberculosis Activities
Kirti T. Patila, Dattatrya K. Jamaleb, Navnath J. Valekarb, Priyanka T. Patila, Poojali P. Warekara, Govind B. Kolekarb and Prashant V. Anbhuleb*.
[email protected]
Tel.: +91 231 260 9169; fax: +91 231 26923aDepartment of Agrochemicals and Pest Management, Shivaji University, Kolhapurb*Medicinal Chemistry Research Lab, Department of Chemistry, Shivaji University,
Kolhapur
Table of content: Page No.
A General Information 01B Typical Procedure 02C Spectral data of of Pyrazolopyranopyrimidine
Derivatives03-27
A. General Information
Melting points were taken in an open glass capillary and are found to be uncorrected.
The desired Structures of all of the compounds were confirmed by their relevant spectral data
IR spectra (KBr) were recorded on a Perkin- Elmer FT-IR Spectrum 100. The 1H NMR and
13C NMR spectra obtained (DMSO-d6) on a Bruker (300 MHz) using TMS as an internal
standard. The progress of reaction was checked by thin layer chromatography (TLC) using
silica gel G (LR). All commercially available chemicals were purchase from sigma Aldrich
and used without purification.
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B. Typical Procedure
To a solution of hydrazine hydrate (0.063 g, 1 mmol) in ethanol (2 mL.) was added ethyl
aceto acetate (0.132 mL., 1 mmol) over 15 min. Next, an 3-nitrobenzaldehyde (0.150, 1
mmol), thiobarbituric acid (0.144g, 1 mmol), were added and the mixture was heated at reflux
temperature for the time indicated in Table 3. After completion of the reaction (as monitored
by TLC), the mixture was cooled and filtered. The precipitate was recrystalised from ethanol
to give pure target compounds. The physical and spectral data of the products as well as their
elemental analysis are given.
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C. Spectral data of Synthesized Compound
(Table 3, Entry 1): 3-methyl-4-(3-nitrophenyl)-7-thioxo- 4, 6, 7, 8 tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5a)
White solid; M. P. 240-2420C. IR (vmax): 3316, 3053, 1617, 1580 cm-1; 1HNMR(300MHz,
DMSO-d6) :δ (ppm): 2.27 (s, 3H, CH3), 5.51 (s, 1H,-CH), 7.52-7.54 (d, 2H, J = 6 Hz, Ar-H),
7.82 (s, 1H, Ar-H), 8.02-8.04 (d, 1H, J = 6 Hz ,Ar-H), 11.57(s, 1H, -NH); 13C NMR
(75MHz, DMSO- d6) :δ (ppm) : 10.37, 31.20, 95.99, 104.71, 121.43, 130.07, 134.22, 144.29,
144.90, 148.14, 159.08,163.89, 173.71 ; HRMS : mass calculated for [C15H11N5O4S] =357.344
[m/z] ; Obs. Mass= m/z= 357.098, (Anal.Calcd for C15H11N5O4S: C (50.42 %), H
(3.10%) ,N( 19.60%); Found: C (50.38%), H (3.08%), N(19.48%) (Fig. S1, S2, S3, S4)
(Table 3, Entry 2): 4-(3,4-dihydroxyphenyl)-3-methyl-7-thioxo-4,6,7,8-tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5b)
White solid; M. P. 244-2460C IR (vmax) :3189, 2879, 1579 cm-1; 1H NMR (300MHz, DMSO-
d6) :δ(ppm): 2.21 (s, 1H, CH3), 5.28 (s, 1H, CH), 6.25-6.27 (d, 1H, J = 6 Hz ,Ar-H), 6.48-6.54
(t, 2H, Ar-H), 8.56 (brs, 1H, OH), 11.24 (s, 1H, -NH) 13C NMR= (75MHz, DMSO- d6): δ
(ppm) 10.28, 30.28, 96.89, 105.89, 114.66, 115.39, 117.90, 133.12, 143.10, 143.79, 144.80,
159.02, 164.15, 172.91; HRMS: mass calculated for [C15H12N4O4S] =344.345 [m/z] ; Obs.
Mass = m/z = 345.077 [M+H]+ , Anal.Calcd for C15H12N4O4S: C (52.32%), H (3.51%) , N
(16.27%); Found: C (52.35%) , H (3.54%), N(16.23%).(Fig. S5, S6, S7, S8)
(Table 3, Entry 3): 4-(3-methyl-5-oxo-7-thioxo-1,4,5,6,7,8-
hexahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-4-yl)benzonitrile (5c)
White solid; M. P. 250-2520C. IR (vmax): 3361, 2576, 2223, 1658 cm-1; 1H NMR (300MHz,
DMSO-d6): δ(ppm) : 2.21 (s, 3H, CH3),5.44 (s, 1H, CH), 7.20-7.23 (d, 2H, J = 9 Hz, Ar-H),
7.48-7.66 (m, 2H, Ar-H), 13C NMR= (75MHz, DMSO-d6): δ (ppm): 10.31, 31.85, 95.76,96.08,
104.31, 108.71, 119.35, 125.99, 128.02, 128.16, 131.85, 142.99, 148.81, 158.89, 164.09, 173.32 ;
HRMS: mass calculated for [C16H11N5O2S] =337.355 [m/z] ; Obs. Mass = m/z= 338.343
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[M+H]+, Anal.Calcd for C16H11N5O2S: C(56.96%), H (3.29%) , N (20.76%), Found: C
(56.91%), H (3.25%), N (20.71%) (Fig. S9, S10, S11, S12)
(Table 3, Entry 4): 4-(4-hydroxyphenyl)-3-methyl-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5d)
White solid; M. P. 250-2520C. IR (vmax: 1567, 2875, 3172, 3247 cm-1; 1H NMR(300MHz,
DMSO-d6) : δ (ppm): 2.18 (s, 1H, CH3), 3.43-3.48 (s, 1H, OH), 5.31 (s, 1H, CH), 6.54-6.57
(d, 2H, J = 9 Hz, Ar-H), 6.82-6.85 (d, 2H, J = 9 Hz, Ar-H), 9.02 (s, 1H, NH), 11.25 (s, 2H,
NH) 13C NMR= (75MHz, DMSO- d6 ): δ (ppm): 0.31, 10.38, 30.45, 96.78, 105.79, 114.95,
127.95, 132.63, 142.79, 155.16, 159.31, 164.04, 172.94, HRMS: mass calculated for
[C15H12N4O3S] =328.345 [m/z] ;Obs. Mass = m/z= 329.324 [M+H]+, Anal.Calcd for
C15H12N4O3S: C (54.87%), H (3.68%), N (17.66%), Found: C (54.83%), H (3.62%),
N(17.61%).(Fig. S13, S14, S15, S16)
(Table 3, Entry 5): 4-(1H-imidazol-2-yl)-3-methyl-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5e)
Cream solid; M. P. 275-2780C. IR (vmax) : 3320, 3107, 2361, 1538, 1442, 1382 cm-1; 1H
NMR (300MHz, DMSO-d6): δ (ppm): 2.13 (s, 3H, CH3), 5.28 (s, 1H,CH), 6.85 (s, 1H, Ar-H),
8.70 (d, 2H, Ar-H), 10.94 (s, 2H, NH), 13C NMR=(75MHz ,DMSO-d6): δ (ppm): 10.50,
25.09, 93.34, 101.99, 115.91, 133.06, 136.89, 138.33, 159.10, 163.90, 173.47 , HRMS : mass
calculated for [C12H10N6O2S] =302.311 [m/z] ; Obs. Mass= 302.306 [m/z] Anal.Calcd for
C12H10N6O2S: C (47.68%), H (3.33%), N(27.80%), Found C (47.62%),H (3.29%),N ( 27.75%)
(Fig. S17, S18, S18, S19)
(Table 3, Entry 6): 3-methyl-4-(3-chlorophenyl)-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5f)
White solid; M. P. 235-2370C. IR (vmax): 1585, 2821, 3413 cm-1; 1H NMR (300MHz, DMSO-
d6) : δ (ppm): 2.20 (s, 3H, CH3), 5.50 (s, 1H, CH), 7.09-7.16 (m, 2H, Ar-H), 7.21-7.23 (d, 1H,
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Ar-H), 7.47-7.50 (d, 1H, J = 9 Hz, Ar-H), 8.17 (s, 1H, NH), 11.13 (s, 1H, NH), 13C NMR=
(75MHz, DMSO-d6): δ (ppm): 10.42, 30.64, 95.67, 104.42, 126.66, 128.20, 130.00, 130.40,
132.89, 139.61, 142.87, 159.33, 163.90, 173.06 , Anal.Calcd for C15H11ClN4O2S : C (51.95%),
H( 3.20%), N(16.16%), Found: C(51.88%), H (3.15%),N (16.10%) (Fig. S20, S21, S22)
(Table 3, Entry 7): 3-methyl-4-(2-chlorophenyl)-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5g)
White solid; M. P. 238-2400C. IR (vmax) : 3287, 3015, 1681, 1586, 1341 cm-1; 1H NMR
(300MHz, DMSO-d6) : δ (ppm): 2.21 (s, 3H, CH3), 5.49 (s, 1H, CH), 7.06-7.19 (q, 3H, Ar-H),
7.43-7.45 (d, 1H, J = 6 Hz ,Ar-H), 13C NMR= (75MHz DMSO-d6): δ (ppm): 10.60, 30.61,
126.13, 127.41, 129.54, 130.58, 133.19, 163.79, 173.11, Anal.Calcd for C15H11ClN4O2S : C
(51.95%), H( 3.20%), N (16.16%), Found: C (51.86%), H (3.18%), N (16.13%) (Fig. S23,
S24, S25)
(Table 3, Entry 8): 3-methyl-4-(2-nitrophenyl)-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5h)
Cream solid; M. P. 244-2450C. IR (vmax) : 3346, 3019, 2351, 1578, 1477 cm-1; 1H NMR
(300MHz, DMSO-d6) : δ (ppm): 2.22 (s, 3H, CH3), 5.78 (s, 1H, CH), 7.29-7.47 (m, 4H, Ar-
H), 10.01 (s, 2H, NH), 13C NMR=(75MHz DMSO-d6) : δ = 10.26, 28.55, 90.79, 105.08,
123.90, 127.54, 130.08, 131.46, 134.75, 144.09, 150.11, 151.54, 159.55, 165.18 ; Anal.Calcd for
C15H11N5O4S: C (50.42%), H (3.10%) N (19.60%), Found: C (50.34%), H, (3.05%) N
(19.46%).(Fig. S26, S27, S28)
(Table 3, Entry 9): 4-(3-hydroxyphenyl)-3-methyl-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5i)
White solid; M. P. 252-2540C. IR (vmax) : 3300, 3219, 2874 cm-1; 1H NMR (300MHz,
DMSO-d6) (Fig.31): δ (ppm): 2.18 (s, 1H, CH3), 5.30 (s, 1H, CH), 6.53-6.56 (d, 2H, J = 9 Hz,
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Ar-H), 6.81-6.84 (d, 2H, J = 9 Hz ,Ar-H), 11.18( s, 2H, NH) 13C NMR= (75MHz DMSO-
d6) : δ (ppm):10.44, 30.52, 56.72, 96.69, 105.75, 114.93, 127.99, 132.83, 142.40, 155.23, 159.43,
164.04, 164.64, 172.99, Anal.Calcd for C15H12N4O3S: C (54.87%), H (3.68%), N (17.66%),
Found: C (54.84%), H (3.64%), N (17.63%) (Fig. S29, S30, S31)
(Table 3, Entry 10): 4-(2-hydroxyphenyl)-3-methyl-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5j)
White solid; M. P. 248-2500C. IR (vmax) : 1612, 2987, 3079, 3183, 3239 cm-1; 1H NMR
(300MHz, DMSO-d6) : δ (ppm): 2.18 (s, 1H, CH3), 3.43-3.48 (d, 1H, OH), 5.30 (s, 1H, CH),
6.54-6.57 (d, 2H, J = 9 Hz, Ar-H), 6.82-6.85 (d, 1H, J = 9 Hz Ar-H), 11.25 ( s, 2H, NH), 13C
NMR=(75MHz, DMSO-d6) : δ (ppm): 10.44, 30.52, 96.63, 105.68, 114.95, 128.01, 132.95,
142.26, 155.25, 159.45, 163.96, 173.00, Anal.Calcd for C15H12N4O3S: C (54.87%) H (3.68%) N
(17.66%), Found: C (54.83%), H (3.65%), N (17.64%) (Fig.S32, S33, S34)
(Table 3, Entry 11): 3-methyl-4-(4-nitrophenyl)-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5k)
Yellow solid; M. P. mp 218-2200C. IR (vmax) : 3334, 3185, 1657, 1517 cm-1; 1H NMR
(300MHz, DMSO-d6) : δ (ppm): 2.26 (s, 3H, CH3), 5.48 (s, 1H, CH), 7.23-7.30 (d, 2H, J = 9
Hz ,Ar-H), 8.04-8.11 (d, 2H, J = 9 Hz, Ar-H),11.56 (s, 2H, NH), 13C NMR= (75MHz,
DMSO-d6) : δ (ppm): 10.29, 18.75, 31.56, 56.60, 95.69, 96.16, 104.75, 123.68, 128.16, 128.37,
144.39, 145.75, 146.13, 150.74, 158.84, 163.99, 173.42, 173.63, (Anal.Calcd for C15H11N5O4S:
C (50.42%), H (3.10%) N(19.60%), Found: C (50.40%), H (3.05%), N(19.50) (Fig.S35, S36,
S37)
(Table 3, Entry 12): 3-methyl-4-(4-chlorophenyl)-7-thioxo-4,6,7,8-
tetrahydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5(1H)-one (5l)
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White solid; M. P. mp 216-2180C. IR (vmax) : 3395, 3317, 2875, 1583, 1517 cm-1; 1H NMR
(300MHz, DMSO-d6) : δ (ppm): 2.20 (s, 3H, CH3), 5.36 (s, 1H, CH), 7.01-7.04 (d, 2H, J = 9
Hz, Ar-H), 7.12-7.15 (d, 2H, J = 9 Hz, Ar-H), 8.05 (s, 1H, NH), 11.19 (s, 2H, NH ),
Anal.Calcd for C15H11ClN4O2S : C (51.95%), H (3.20%), N (16.16%), Found: C (51.90%), H
(3.16%) N (16.11%) (Fig. S38, S39)
IR spectra of 5a
Fig. S1
1HNMR of 5a
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Fig. S2
13CNMR of 5a
Fig. S3
Mass Spectra of 5a
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Fig.S4
IR spectra of 5b
Fig.S5
1HNMR of 5b
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Fig. S6
13CNMR of 5b
Fig. S7
Mass spectra of 5b
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Fig. S8
IR spectra of 5c
Fig. S9
1HNMR of 5c
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Fig. S10
13CNMR of 5c
Fig. S11
Mass Spectra of 5c
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Fig. S12
IR spectra of 5d
Fig. S13
1HNMR of 5d
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Fig. S14
13CNMR of 5d
Fig. S15
Mass spectra of 5d
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Fig. S16
IR spectra of 5e
Fig. S17
1HNMR of 5e
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Fig. S18
13CNMR of 5e
Fig. S19
Mass Spectra of 5e
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Fig. S20
Mass Spectra of 5f
Fig. S21
1HNMR of 5f
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Fig. S22
13CNMR of 5f
Fig. S23
IR spectra of 5g
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Fig. S24
1HNMR of 5g
Fig. S25
13CNMR of 5g
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Fig. S25
IR spectra of 5h
Fig. S26
1HNMR of 5h
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Fig. S27
13CNMR of 5h
Fig. S28
IR spectra of 5i
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Fig. S29
1HNMR of 5i
Fig. S30
13CNMR of 5i
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Fig. S31
IR Spectra of 5j
Fig. S32
1HNMR of 5j
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Fig. S33
13CNMR of 5j
Fig. S34
IR spectra of 5k
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Fig. S35
1HNMR of 5k
Fig. S36
13CNMR of 5k
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Fig. S37
IR Spectra of 5l
Fig. S38
1HNMR of 5i
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