224 JOURNAL OF CHEMICAL RESEARCH 2017
corresponding sulfonyl chloride (a–c) (0.9 equiv.) was added slowly
for about 5 min at 10–15 °C. The reaction mass temperature was raised
to about 25 °C and stirred for 2 h. After reaction completion (monitored
by TLC), the reaction mass was quenched with 5% sodium bicarbonate
solution (6 vol.), extracted into DCM (10 vol.), washed with water (5 vol.)
and brine solution (5 vol.), and then dried over anhydrous sodium sulfate
and concentrated completely to obtain the desired products 2a–c as solids.
N’-(6,6-Dimethyl-9-oxo-4,5,6,7,8,9-hexahydropyrazolo[5,1-b]
quinazoline-3-carbonyl)-2-fluorobenzenesulfonohydrazide (2a): Off-
3-(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-5,6,7,8-
tetrahydropyrazolo[5,1-b]quinazolin-9(4H)-one (3b): Off-white solid;
1
yield 56%; H NMR (400 MHz, DMSO-d ): δ 0.99 (s, 6H), 1.44–1.48 (t,
6
2
3
)
2
(
3
1
H, J = 6.4 Hz, J = 6.8 Hz), 2.41–2.45 (t, 2H, J = 6.0 Hz, J = 6.0 Hz),
1
2
1
2
.28 (s, 2H), 4.1 (bs, 1H), 7.62–7.65 (m, 2H), 7.81–7.83 (d, 1H, J = 8.8 Hz
13
, 8.91 (s, 1H), 12.03 (s, 1H); C NMR (75 MHz, DMSO-d ): δ 19.7, 27.9,
6
9.3, 34.2, 96.6, 105.1, 129.7, 129.8, 138.3, 141.3, 147.8, 156.2; IR (ATR)
−1
υ cm ): 751, 851, 1479, 1496, 1634, 2859, 2950, 3438; LCMS (ESI) m/z:
+
96.0 Da ([M + H] ). Anal. calcd for C H ClN O : C, 60.68; H, 4.58; N,
1
20 18 5 2
white solid; yield 78%; H NMR (400 MHz, DMSO-d ): δ 0.94 (s, 6H),
6
7.69; found : C, 60.65; H, 6.15; N, 17.70%.
1
.22 (s, 4H), 1.46 (s, 4H), 7.3–7.34 (m, 1H), 7.39–7.44 (m, 1H), 7.68–7.7 (m,
3
-(5-(3,5-Dimethylphenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-
13
1H), 7.78–7.82 (m, 1H), 8.29 (s, 1H), 10.12 (s, 1H), 10.39 (s, 1H); C NMR
5
,6,7,8,-tetrahydropyrazolo[5,1-b]quinazolin-9(4H)-one (3c): Off-white
(
100 MHz, DMSO-d ): δ 19.7, 27.9, 29.4, 96.6, 105.1, 117.6–117.9, 124.9,
6
1
solid; yield 66%; H NMR (400 MHz, DMSO-d ): δ 1.0 (s, 6H), 1.52–1.55
6
1
27.9, 130.6, 136.1–136.2, 141.2, 142.9, 147.8, 156.2, 158.1, 160.6, 161.4; IR
−1
(m, 2H), 2.39 (s ,6H), 2.49–2.5 (m, 2H), 2.62 (s, 2H), 7.27 (s, 1H), 7.75 (s,
(ATR) (υ cm ): 829, 1198, 1300, 1597, 1634, 1686, 1817, 2961, 3147, 3367;
1
3
+
2H), 8.47 (s, 1H), 12.0 (bs, 1H, NH); C NMR (100 MHz, DMSO-d ):
LCMS (ESI) m/z: 434.3 Da ([M + H] ). Anal. calcd for C H FN O S:
6
19
20
5
4
−1
δ 21.2, 27.9, 29.4, 88.9, 124.6, 133.7; IR (ATR) (υ cm ): 635, 1194, 1582,
612, 1701, 2935, 3431; LCMS (ESI) m/z: 390.1 Da ([M + H] ). Anal. calcd
C, 52.65; H, 4.65; N, 16.16; S, 7.40; found: C, 52.61; H, 4.69; N, 16.15; S,
.43%.
-Chloro-N’- (6,6-dimethyl-9-oxo-4,5,6,7,8,9-hexahydro-
pyrazolo[5,1-b]quinazoline-3-carbonyl)benzenesulfonohydrazide
+
1
7
for C H N O : C, 67.85; H, 5.95; N, 17.98; found: C, 67.82; H, 6.04; N,
2
22 23
5
2
17.95%.
1
(
2b): Off-white solid; yield 85%; H NMR (400 MHz, DMSO-d ):
6
Acknowledgements
δ 0.97 (s, 6H), 1.44–1.47 (t, 2H, J = 6.4 Hz, J = 6.4 Hz), 2.41–2.44 (t,
1
2
2
H, J = 6.0 Hz, J = 6.0 Hz), 3.16 (s, 2H), 4.1 (bs, 1H), 7.45–7.5 (m,
We thank the Management, Anthem Biosciences, Bangalore,
India, for their invaluable support and allocation of resources for
this work. We thank the analytical chemistry team of Anthem
Biosciences for carrying out all the analytical work.
1
2
1H), 7.3–7.34 (m, 1H), 7.39–7.44 (m, 1H), 7.61–7.67 (m, 1H), 7.98–8.0
13
(m, 1H), 8.29 (s, 1H), 10.0 (s, 1H), 10.3 (s, 1H); 11.4 (s, 1H); C NMR
(100 MHz, DMSO-d ): δ 19.7, 27.9, 29.3, 34.2, 96.8, 105.1, 127.8, 131.3,
6
132.1, 132.3, 134.7, 137.8, 141.3, 142.9, 147.9, 156.2, 161.5; IR (ATR) (υ
−1
cm ): 861, 1045, 1297, 1597, 1641, 1686, 2929, 3181, 3371, 3628; LCMS
Electronic Supplementary Information
+
(
ESI) m/z: 450.4 Da ([M + H] ). Anal. calcd for C H ClN O S: C,
19 20 5 4
The ESI is available from:
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
50.72; H, 4.48; N, 15.57; S, 7.13; found: C, 50.70; H, 4.51; N, 15.54; S,
7
.14%.
-Chloro-N’- (6,6-dimethyl-9-oxo-4,5,6,7,8,9-hexahydro-
pyrazolo[5,1-b]quinazoline-3-carbonyl)benzenesulfonohydrazide
4
Received 16 January 2017; accepted 27 February 2017
Paper 1704539
Published online: 3 April 2017
1
(2c): Off-white solid; yield 76%; H NMR (400 MHz, DMSO-d ): δ
6
0.99 (s, 6H), 1.44–1.48 (t, 2H, J = 6.4 Hz, J = 6.8 Hz), 2.41–2.45 (t, 2H,
1
2
J = 6.0 Hz, J = 6.0 Hz), 3.28 (s, 2H), 4.1 (bs, 1H), 7.62–7.65 (m, 2H),
1
2
7.81–7.83 (d, 1H, J = 8.8 Hz ), 8.3 (s, 1H), 10.0 (s, 1H), 10.3 (s, 1H); 11.4
13
(
1
s, 1H); C NMR (75 MHz, DMSO-d ): δ 19.7, 27.9, 29.3, 34.2, 96.6,
6
−1
05.1, 129.7, 129.8, 138.3, 141.3, 147.8, 156.2; IR (ATR) (υ cm ): 734,
1
R. Elie, E. Rüther, I. Farr, G. Emilien and E. Salinas, J. Clin. Psychiatry, 1999,
0, 536.
1168, 1327, 1597, 1628, 1682, 2927, 3181, 3246, 3574; LCMS (ESI) m/z:
6
+
450.0 Da ([M + H] ). Anal. calcd for C H ClN O S: C, 50.72; H, 4.48;
19 20 5 4
2
3
M. Baumann, I.R. Baxendale, Beil. J. Org. Chem., 2013, 9, 2265.
P. Ackermann, P. Margot and F. Müller, “Fungicides, Agricultural”, Ullmann’s
Encyclopedia of Industrial Chemistry., Electronic Release, Wiley-VCH,
Weinheim, 2000
N, 15.57; S, 7.13; found: C, 50.71; H, 4.52; N, 15.55; S, 7.11%.
Synthesis of 1,3,4-oxadiazoles (3a–c); general procedure
To a solution of 1 (10 mol) in DMF (6 vol.), dicyclohexylcarbodiimide
4
5
E.B. Mark, P.M. John, D.A.S. Stephen and W. Anthony, U.S. Patent: 6670366
B1, issued 30 December 2003.
(15 mol) was added under inert atmosphere at about 5 °C. The resultant
solution was stirred for 1 h at the same temperature. To this solution,
the corresponding acid chloride (10 mol) was added and stirred for
S.D. Sawant, G. LakshmaReddy, M.I. Dar, M. Srinivas, G. Gupta, P.K. Sahu,
P. Mahajan, A. Nargotra, S. Singh, S.C. Sharma, M. Tikoo, G. Singh, R.A.
Vishwakarma and S.H. Syed, Bioorg. Med. Chem., 2015, 23, 2121.
A.T. Baviskar, U.C. Banerjee, M. Gupta, R. Singh, S. Kumar, M.K. Gupta, S.
3
0 min. Then the reaction mass was slowly brought to ambient temperature
followed by heating to 110 °C for 10 h. After reaction completion
monitored by TLC), the reaction mass was poured into ice cold water
6
7
(
006, 5, 689.
and the precipitated side product (dicyclohexyl urea) was separated out by
filtration and washed with ethyl acetate (10 vol.). Layers were separated
and the aqueous layer was back extracted with ethyl acetate (10 vol.). The
combined organic layer was washed with brine, dried over with sodium
sulfate and concentrated under reduced pressure to obtain the crude
product, which was purified by column chromatography using ethyl
acetate–hexanes in a gradient manner to obtain the desired products 3a–c
as solids.
2
8
9
M.M. Anthony and J.D. Roger, Nat. Rev. Drug Discov., 2003, 2, 554.
T. Sekiya, H. Hiranuma, M. Uchide, S. Hata and S. Yamada, Chem. Pharm.
Bull., 1981, 29, 948.
10 R.K. John, L. Huaqing, D. Irene, G.W. David, L.C. Tracy, M.M. Arlene, M.
1
1
B.E. Gilbert and V. Knight, Antimicrob. Agents Chemother., 1986, 30, 201
M.F. Hebert and B.J. Guglielmo, Drug Intell. Clin. Pharm., 1990, 8, 735.
3 J.C. Fackler, K. Flannery, M. Zipkin and K. McIntosh, J. Med., 1990, 9, 634.
3
-(5-(4-Fluorophenyl)-1,3,4-oxadiazol-2-yl)-6,6-dimethyl-5,6,7,8-
1
2
tetrahydropyrazolo[5,1-b]quinazolin-9(4H)-one (3a): Off-white solid;
1
1
yield 62%; H NMR (400 MHz, DMSO-d ): δ 1.04 (s, 6H), 1.72–1.79 (m,
6
14 T. Sekiya, H. Hiranuma, M. Uchide, S. Hata and S. Yamada, Chem. Pharm.
Bull., 1981, 29, 948.
15
2
H), 2.86 (s, 2H), 2.88–2.92 (m, 2H), 7.48–7.52 (m, 2H), 8.14–8.17 (m
−1
,2H), 8.91 (s, 1H); IR (ATR) (υ cm ): 751, 851, 1479, 1496, 2924, 2950,
+
2014, 25, 2081.
3438; LCMS (ESI) m/z: 378 Da ([M − H] ). Anal. calcd for C H FN O :
20 18 5 2
C, 63.32; H, 4.78; N, 18.46; found: C, 63.30; H, 4.82; N, 18.44%.
16 D. Gerlier and N. Thomasset, J. Immunol. Methods, 1986, 94, 57.