194
F. A. El-Essawy and A. S. El-Etrawy
Vol 51
(s, 3H, OCH3), 7.09–7.31 (m, 3H, ArH), 7.35–7.39 (m, 3H, ArH),
7.41–9.11 (m, 2H, ArH), 11.53 (bs, 1H, NH); 13C NMR (DMSO-
d6): d = 7.43, 7.67 (2 CH3CH2), 23.50, 23.87 (2 CH3CH2), 51.77
(OCH3), 79.20 (C-5), 97.76 (CN), 115.85 (2C), 117.62, 118.92,
120.12, 120.54, 120.68, 121.77, 127.77, 129.69 (2C), 135.88,
144.64, 153.80, 153.92, 156.99 (Ar–C), 163.77 (CO); MS (EI):
m/z 387 (M+ + 1, 10), 386 (M+, 50), 298 (100). Anal. Calcd for
C24H22N2O3C: 74.59; H, 5.74; N, 7.25. Found: C, 74.70; H, 5.83;
2-Chloro-5-ethyl-5-methyl-4-p-tolyl-5H-chromeno[4,3-b]pyridine-
3-carbonitrile (5b). Yield 2.33 g 62%; mp 118–119ꢀC; IR (KBr)
n 2217 (CN), 1566 (N═C)cmÀ1 1H NMR (MHz, CDCl3):
;
d = 1.12 (t, 3H, J = 7.5Hz, CH3CH2), 1.32 (s, 3H, CH3), 2.21
(q, 2H, J = 7.5Hz, CH3CH2), 2.44 (s, 3H, CH3C6H4), 7.30–7.41
(m, 5H), 7.56–7.84 (m, 3H, ArH); MS (EI): m/z 375 (M+ + 1, 25),
374 (M+, 60), 279 (100). Anal. Calcd for C23H19ClN2O: C, 73.69;
H, 5.11; N, 7.47; Found: C, 73.88; H, 5.04; N, 7.65.
2.1.3 2-Chloro-5,5-diethyl-4-p-tolyl-5H-chromeno[4,3-b]pyridine-
N, 7.45.
4-(4-Chlorophenyl)-5,5-dimethyl-2-oxo-2,5-dihydro-1H-chro-
3-carbonitrile (5c). Yield 2.73 g (70%); mp 88–90ꢀC;. IR (KBr)
n 2219 (CN), 1550 (N═C)cmÀ1; 1H NMR (MHz, CDCl3): d 1.00
(t, 3H, CH3CH2), 1.18 (t, 3H, CH3CH2), 1.73–2.36 (m, 4H,
2 CH3CH2), 2.47 (s, 3H, CH3C6H4), 7.20–7.35 (m, 5H, ArH),
7.42–7.66 (m, 3H, ArH); MS (EI): m/z 389 (M+ + 1, 5), 388 (M+,
20), 332 (70), 280 (100). Anal. Calcd for C24H21ClN2O: C, 74.12;
H, 5.44; N, 7.20. Found: C, 74.22; H, 5.61; N, 7.12.
meno[4,3-b]pyridine-3-carbonitrile (4g). Pale yellow powder,
yield 3.1g (85%); mp 190–191ꢀC; IR (KBr) n 3284 (NH),
2212 (CN), 1650 (CO) cmÀ1 1H NMR (DMSO-d6): d 1.50
;
(s, 3H, CH3), 1,52 (s, 3H, CH3), 7.53–7.63 (m, 3H, ArH), 7.69–
8.22 (m, 5H, ArH), 13.65 (, bs, 1H, NH); MS (EI): m/z 362
(M+, 30), 297 (100). Anal. Calcd for C21H15ClN2O2C, 69.52; H,
4.17; N, 7.72. Found: C,69.73; H, 4.22; N, 7.85.
4-(4-Chlorophenyl)-5-ethyl-5-methyl-2-oxo-2,5-dihydro-1H-
General procedure for the syntheses of 6,6-dialkyl-7-p-tolyl-
6,10-dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridin-8-amine
(6a–c). A mixture of choropyridochromane derivatives 5a–c
(10 mmol) and 1.25 g hydrazine hydrate (25 mmol) in 30 mL
ethanol was heated under reflux for 4–6 h. The excess ethanol
was removed under reduced pressure and the resulting
precipitate was filtered off, washed with ethanol, and
recrystallized from methanol-DMF to give bright orange solid
chromeno[4,3-b]pyridine-3-carbonitrile (4h). Yellow crystal, yield
3.45g (92%); mp 150–151ꢀC; IR (KBr) n 3274 (NH), 2206 (CN),
1
1644 (CO) cmÀ1; H NMR (DMSO-d6): d 1.10 (t, 3H, J = 7.5Hz,
CH3CH2), 1.25 (s, 3H, CH3), 2.29 (q, 2H, J = 7.5 Hz, CH3CH2),
7.50–7.58 (m, 3H, ArH), 7.60–7.87 (m, 5H, ArH), 13.05 (bs, 1H,
NH); 13C NMR (DMSO-d6): d 7.55 (CH3CH2), 21.74 ( CH3),
28.56 (CH2CH3), 83.96 (C-5), 108.88 (CN), 116.58, 117.74 (2C),
118.94, 118.98, 119.17, 120.30, 120.67, 121.71, 121.74, 121.81,
135.80 (2C), 144.29, 149.12, 152.70 (Ar–C), 168.76 (CO); MS
(EI): m/z 377 (M+ + 1, 25), 376 (M+, 30), 347 (100). Anal. Calcd
for C22H17ClN2O2C, 70.12; H, 4.55; N, 7.43. Found: C,70.31; H,
of 6a–c.
6,6-Dimethyl-7-p-tolyl-6,10-dihydrochromeno[4,3-b]pyrazolo
[4,3-e]pyridin-8-amine (6a). Yield 2.67 g (75%); mp 315–
316ꢀC;.IR (KBr) n 3380–3270 (NH, NH2),1615 (N═C) cmÀ1
;
1H NMR (DMSO-d6): d 1.45 (s, 3H, CH3), 1,49 (s, 3H, CH3),
2.57 (s, 3H, CH3C6H4), 5.40 (bs, 2H, NH2), 7.11–7.20 (m, 3H,
ArH), 7.66–8.03 (m, 5H, ArH), 11.99 (bs, 1H, NH); 13C NMR
(DMSO-d6): d 21.61, 22.06, 26.43 (3 CH3), 78.97 (C-5),
118.14, 118.57, 120.47, 121.45, 123.86 (2C), 128.47, 138.29,
129.30 (2C), 136.35, 140.94, 141.86, 142.79, 145.55, 147.13,
149.55, 154.81 (Ar–C); MS (EI): m/z 357 (M+ + 1, 35), 356
(M+ + 75), 315 (55), 238 (100). Anal. Calcd for C22H20N4O: C,
74.14; H, 5.66; N, 15.72. Found: C, 74.05; H, 5.76; N, 15.42.
6-Ethyl-6-methyl-7-p-tolyl-6,10-dihydrochromeno[4,3-b]pyrazolo
[4,3-e]pyridin-8-amine (6b). Yield 2.47 g 67%; mp 288–290ꢀC; IR
4.70; N, 7.55.
4-(4-Chlorophenyl)-5,5-diethyl-2-oxo-2,5-dihydro-1H-chromeno
[4,3-b]pyridine-3-carbonitrile (4i). Yellow crystal, mp 130–132ꢀC;
1
IR (KBr) n 3270 (NH), 2214 (CN), 1643 (CO) cmÀ1; H NMR
(DMSO-d6): d 0.98–1.04 (m, 6H, 2 CH3CH2), 2.22–2.28
(m, 4H, 2 CH3CH2), 7.48–7.55 (m, 3H, ArH), 7.61–8.19
(m, 5H, ArH), 12.86 (bs, 1H, NH); MS (EI): m/z 391
(M+ + 1, 16), 317 (15), 296 (70), 125 (100). Anal. Calcd for
C23H19ClN2O2: C, 70.68; H, 4.90; N, 7.17. Found: C,79.52; H,
4.75; N, 7.08.
(KBr) n 3320–3250 (NH, NH2), 1605 (N═C)cmÀ1
;
1H NMR
General procedure for the syntheses of 2-chloro-5,5-
(DMSO-d6): 0.99 (t, 3H, J = 7.5Hz, CH3CH2), 1.40
d
dialkyl-4-p-tolyl-5H-chromeno[4,3-b]pyridine-3-carbonitrile
(5a–c). Chromenopyridine derivatives 4a–c (10 mmol) were
added to an amount corresponding to five times their
weight of POCl3, and the mixture was refluxed until the
starting material had disappeared at TLC analysis (eluent
toluene/acetone 8:2). The suspension was then cooled first
to room temperature and poured carefully into water/ice
with stirring. The resulting precipitate was collected,
washed many times with water, dried and recrystallized
from hexane-THF afforded a pale yellow powder of 5a–c
in good yields.
(s, 3H, CH3), 1.85 (q, 2H, J = 7.5Hz, CH3CH2), 2.51 (s, 3H,
CH3C6H4), 5.78 (s, 2H, NH2), 7.06–717 (m, 5H, ArH), 7.49–7.83
(m, 3H, ArH); 11.77 (bs, 1H, NH); MS (EI): m/z 371 (M+ + 1,
10), 370 (M+, 35), 328 (100). Anal. Calcd for C23H22N4O:
C, 74.57; H, 5.99, N, 15.12. Found: C, 74.45; H, 6.03; N, 15.25.
6,6-Diethyl-7-p-tolyl-6,10-dihydrochromeno[4,3-b]pyrazolo[4,3-e]
pyridin-8-amine (6c). Yield 3.84 g (72%); mp 277–278ꢀC; IR
(KBr) n 3299–3188 (NH, NH2), 1587 (N═C)cmÀ1 1H NMR
;
(DMSO-d6): d 0.95–1.22 (m, 6H, 2 CH3CH2), 1.80–2.25 (m, 4H,
2 CH3CH2), 2.57 (s, 3H, CH3C6H4), 5.09 (bs, 2H, NH2), 6.76–
7.09 (m, 5H, ArH), 7.26–7.67 (m, 3H, ArH), 11.54 (bs, 1H, NH);
MS (EI): m/z 385 (M+ + 1, 25), 384 (M+, 55), 355 (15), 310 (100).
Anal. Calcd for C24H24N4O: C, 74.97; H, 6.29; N, 14.57. Found:
C, 74.75; H, 6.17; N, 14.69.
General procedure for the syntheses of N-substituted
benzylidine-7-p-tolyl-dihydrochromeno[4,3-b]pyrazolo[4,3-e]
pyridin-8-amine (7a–d). A mixture of 0.360 g 6a (1 mmol), an
appropriate aromatic aldehydes (1 mmol), 10 mL dioxane and
0.3 mL piperidine was refluxed for 6 h. The solid product,
which formed, was collected by filtration and recrystallized
from suitable solvent to give 7a–c.
2-Chloro-5,5-dimethyl-4-p-tolyl-5H-chromeno[4,3-b]pyridine-
3-carbonitrile (5a). Yield 2.65 g (73%); mp 112.0–114.0ꢀC; IR
1
(KBr) n 2222 (CN),1570 (N═C)cmÀ1; H NMR (MHz, CDCl3):
d 1.53 (s, 3H, CH3), 1.55 (s, 3H, CH3), 2.45 (s, 3H, CH3C6H4),
7.13–7.36 (m, 3H, ArH), 7.67–7.92 (m, 5H, ArH); 13C NMR
(MHz, CDCl3): d = 20.28, 21.61, 24.15 (3 CH3), 85.38 (C-5),
109.91 (CN), 117.56, 118.36, 118.98, 119.44, 121.78, 122.0.55,
128.47 (2C), 129.32 (2C), 136.35, 141.86, 142.33, 145.40,
148.66, 149.55, 156.49 (Ar–C); MS (EI): m/z 361 (M+, 70), 360
(100). Anal. Calcd for C22H17ClN2O: C, 73.23; H, 4.75; N, 7.76;
Found C, 73.12; H, 4.43; N, 7.57.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet