Vol 49
854
C. N. Revanna, T. R. Swaroop, G. M. Raghavendra, D. G. Bhadregowda, K. Mantelingu, and
K. S. Rangappa
C16H13ClN3O4: C, 61.73; H, 4.21; H, 4.50; N, 13.50. Found:
C, 61.68; H, 4.25; H, 4.50; N, 13.45.
2‐Amino‐4‐(2‐fluorophenyl)‐5,6,7,8‐tetrahydro‐5‐oxo‐4H‐
chromene‐3‐carbonitrile (4m). White solid. Yield 1.04 g
(82%). mp 224–225°C. IR (KBr): 3325.5, 3175.8, 2190.9,
1684.2, 1647.1, 1370.1, 1211.0. 1H NMR (400 MHz, DMSO‐
d6): δ 1.88–1.20 (m, 2H, CH2), 2.19–2.34 (m, 2H, CH2), 2.63
(m, 2H, CH2), 4.46 (s, 1H, CH), 7.02 (s, 2H, NH2), 7.07–7.25
(m, 4H, Ar‐H). MS (ESI + ion): m/z = 285.2. Anal. Cacld for
C16H13FN2O2: C, 67.60%; H, 4.61; N, 9.85. Found: C, 67.67;
H, 4.65; N, 9.88.
2‐Amino‐5,6,7,8‐tetrahydro‐5‐oxo‐4‐biphenyl‐4H‐chromene‐
3‐carbonitrile (4g). White solid. Yield 1.46 g (96%). mp 232–
234°C. IR (KBr): 3434.5, 3324.4, 2067.2, 1679.0, 1649.6,
1
1363.7, 1200.4. H NMR (400 MHz, DMSO‐d6): δ 1.89–2.00
(m, 2H, CH2), 2.23–2.32 (m, 2H, CH2), 2.61 (m, 2H, CH2),
3
4.22 (s, 1H, CH), 7.03 (d, 2H, NH2), 7.24 (d, JH,H = 8.2 Hz,
3
3
1H, Ar‐H), 7.35 (t, JH,H = 7.2 Hz, 2H, Ar‐H), 7.44 (t, JH,H
=
3
7.6Hz, 2H, Ar‐H), 7.57 (d, JH,H = 8.2 Hz, 2H, Ar‐H), 7.62
(d, JH,H = 7.8 Hz, 2H, Ar‐H). MS (ESI + ion): m/z = 343.2.
2‐Amino‐4‐(1,4‐dihloro‐1H‐pyrazol‐3‐yl)‐5,6,7,8‐tetrahydro‐
5‐oxo‐4H‐chromene‐3‐carbonitrile (4n). White solid. Yield
1.11 g (82%). mp 245–247°C. IR (KBr): 3387.4, 3293.6,
3
Anal. Cacld for C22H18N2O2: C, 61.73; H, 4.21; H, 4.50; N,
13.50. Found: C, 61.73; H, 4.21; H, 4.50; N, 13.50.
1
2196.1, 1678.9, 1657.1, 1363.3. H NMR (400 MHz, DMSO‐
Amino‐5,6,7,8‐tetrahydro‐5‐oxo‐4‐(2‐oxo‐2H‐chromen‐8‐yl)‐
4‐chromen‐3‐carbonitrile (4h). White solid. Yield 1.34 g
(90%). mp 198–200°C. IR (KBr): 3323.1, 3205.9, 2187.3,
1729.2, 1643.4, 1365.5. 1H NMR (400 MHz, DMSO‐d6): δ
1.85–1.94 (m, 2H, CH2), 2.20–2.30 (m, 2H, CH2), 2.61
d6): δ 1.83–1.99 (m, 2H, CH2), 2.21–2.30 (m, 2H, CH2), 2.56
(m, 2H, CH2), 3.71 (s, 3H, N CH3), 4.33 (s, 1H, CH), 6.97
(s, 2H, NH2), 7.75 (s, 1H, Ar‐H). MS (ESI + ion): m/z =
305.0. Anal. Cacld for C14H13ClN4O2: C, 55.18; H, 4.30; N,
18.39. Found: C, 55.23; H, 4.32; N, 18.88.
3
(m, 2H, CH2), 4.27 (s, 1H, CH), 6.45 (d, JH,H = 9.6 Hz, 1H,
2‐Amino‐5,6,7,8‐tetrahydro‐4‐(isoquinolin‐8‐yl)‐5‐oxo‐4H‐
3
Ar‐H), 7.08 (s, 2H, NH2), 7.32 (d, JH,H = 8.5 Hz, 1H, Ar‐H),
chromene‐3‐carbonitrile (4o).
White solid. Yield 1.15 g
3
7.41 (d, 1H, Ar‐H), 7.51 (s, 1H, Ar‐H), 8.08 (d, JH,H = 9.6 Hz,
(82%). mp 232–235°C. IR (KBr): 3815.8, 3576.5, 3298.8,
2958.1, 2175.1, 1598.7, 1359.1, 1210.9. 1H NMR (400 MHz,
DMSO‐d6): δ 1.94–2.00 (m, 2H, CH2), 2.16–2.32 (m, 2H,
CH2), 2.65–2.74 (m, 2H, CH2), 5.11 (s, 1H, CH), 7.03 (s, 2H,
1H, Ar‐H). MS (ESI + ion): m/z =335.2.2. Anal. Cacld
for C19H14N2O4S: C, 68.26; H, 4.22; N, 8.38. Found: C,
68.29; H, 4.18; N, 8.43.
3
3
2‐Amino‐5,6,7,8‐tetrahydro‐5‐oxo‐4‐(thiazol‐4‐yl)‐4H‐
chromene‐3‐carbonitrile (4i). White solid. Yield 1.17 g (96%). mp
220–223°C. IR (KBr): 3395.4, 3310.5, 3203.1, 2175.4, 1674.2,
1643.5, 1358.8, 1259.4. 1H NMR (400 MHz, DMSO‐d6): δ
1.8–1.98 (m, 2H, CH2), 2.2–2.35 (m, 2H, CH2), 2.60 (m, 2H,
CH2), 4.43 (s, 1H, CH), 7.00 (s, 2H, NH2), 7.36 (s, 1H, Ar‐H),
8.94 (s, 1H, Ar‐H). MS (ESI + ion): m/z = 274.2. Anal. Cacld
for C13H11N3O2S: C, 57.13; H, .4.06; N, 15.37. Found: C,
57.13; H, 4.06; N, 15.37.
NH2), 7.54 (d, JH,H = 7.3 Hz, 1H, Ar‐H), 7.62 (t, JH,H = 8.0
3
Hz, 1H, Ar‐H), 7.98 (d, JH,H = 8.0 Hz, 1H, Ar‐H), 8.21
3
3
(d, JH,H = 6.1 Hz, 1H, Ar‐H), 8.53 (d, JH,H = 6.1 Hz, 1H,
Ar‐H), 9.30 (s, 1H, Ar‐H). MS (ESI + ion): m/z = 318.2. Anal.
Cacld for C19H15N3O2: C, 71.91%; H, 4.76; N, 13.24. Found:
C, 71.95; H, 4.79; N, 13.28.
2‐Amino‐5,6,7,8‐tetrahydro‐4‐(napthalen‐1‐yl)‐5‐oxo‐4H‐
chromene‐3‐carbonitrile (4p).
White solid. Yield 1.15 g
(82%). mp 223–225°C. IR (KBr): 3452.5, 3327.2, 2197.3,
1663.8, 1598.1, 1357.6. 1H NMR (400 MHz, DMSO‐d6): δ
1.91–2.02 (m, 2H, CH2), 2.16–2.33 (m, 2H, CH2), 2.48–2.74
(m, 2H, CH2), 5.14 (s, 1H, CH), 6.93 (s, 2H, NH2), 7.24
2‐Amino‐4‐(4‐cyanophenyl)‐5,6,7,8‐tetrahydro‐5‐oxo‐4H‐
chromene‐3‐carbonitrile (4j). White solid. Yield 1.26 g
(97%). mp 215–217°C. IR (KBr): 3324.5, 3173.2, 3211.7,
2925.3, 2186.5, 1679.5, 1364.5, 1208. 1H NMR (400 MHz,
DMSO‐d6): δ 1.87–1.98 (m, 2H, CH2), 2.24–2.34 (m, 2H,
CH2), 2.61 (m, 2H, CH2), 4.28 (s, 1, CH), 7.14 (s, 2H, NH2),
3
3
(d, JH,H = 6.8 Hz, 1H, Ar‐H), 7.43 (t, JH,H = 8.0 Hz, 1H,
3
Ar‐H), 7.49–7.58 (m, 2H, Ar‐H), 7.76 (d, JH,H = 8.1 Hz, 1H,
Ar‐H), 7.91 (d, JH,H = 7.9 Hz, 1H, Ar‐H), 8.37 (d, JH,H
3
3
=
3
3
7.36 (d, JH,H = 8.3 Hz, 2H, Ar‐H), 7.75 (d, JH,,H = 8.3 Hz,
2H, Ar‐H). MS (ESI + ion): m/z = 292.2. Anal. Cacld for
C17H13N3O2: C, 70.09%; H, 4.50; N, 14.42. Found: C, 70.18;
H, 4.54; N, 14.38.
8.4 Hz, 1H, Ar‐H). MS (ESI + ion): m/z = 316.0. Anal. Cacld
for C20H16N2O2: C, 75.93%; H, 5.10; N, 8.85. Found: C,
75.95; H, 5.18; N, 8.88.
2‐Amino‐4‐(4‐(dimethylamino)phenyl)-5-oxo-5,6,7,8‐
tetrahydro‐5‐4H‐chromene‐3‐carbonitrile (4k). White solid.
Yield 1.16 g (84%). mp 222–225°C. IR (KBr): 3324.5, 3173.2,
3211.7, 2925.3, 2186.5, 1679.5, 1364.5, 1208. 1H NMR (400 MHz,
DMSO‐d6): δ 1.81–1.96 (m, 2H, CH2), 2.19–2.29 (m, 2H, CH2),
Acknowledgments. KSR acknowledges BRNS vide no. 2009/37/
40/BRNS/2266 dated 23‐11‐2009.
3
2.50 (m, 2H, CH2), 4.05 (s, 1H, CH), 6.63 (d, JH,H = 8.7 Hz, 2H,
REFERENCES AND NOTES
3
Ar‐H), 6.87 (s, 2H, NH2), 6.94 (d, JH,H = 8.7 Hz, 2H, Ar‐H). MS
[1] (a) Domling, A.; Ugi, I. Angew Chem Int Ed 2000, 39,
3168; (b) Brase, S.; Gil, C.; Knepper, K. Bioorg Med Chem 2002, 10,
2415; (c) Orra, R. V. A.; de Greef, M. Synthesis 2003, 10, 1471; (d)
Balme, G.; Bosshharth, E.; Monteiro, N. Eur J Org Chem 2003, 21, 4101.
[2] Bonsignore, L.; Loy, G.; Secci, D.; Caligano, A. Eur J Med
Chem 1993, 28, 517.
[3] (a) Begaley, P.; Blackie, M. A. L.; Chibale, K.; Clakson,
C.; Meijiboom, R.; Moss, J. R.; Smith, P.; Su, H. Dalton Trans 2003,
15, 3046; (b) Bolognese, A.; Correale, G.; Manfra, M.; Lavecchia, A.;
Mazzoni, O.; Novelono, E.; La Colla, P.; Sanna, G.; Loddo, R. J Med
Chem 2004, 47, 849.
(ESI + ion): m/z = 310.2. Anal. Cacld for C18H19N3O2: C, 69.88%;
H, 6.19; N, 13.58. Found: C, 69.83; H, 6.16; N, 13.61.
2‐Amino‐5,6,7,8‐tetrahydro‐5‐oxo‐4‐p‐tolyl‐4‐chromene‐3‐
carbonitrile (4l).
White solid. Yield 1.05 g (84%). mp 219–
221°C. IR (KBr): 3408.9, 3332.1, 3257.8, 2195.8, 1683.0,
1659.2, 1366.0. 1H NMR (400 MHz, DMSO‐d6): δ 1.83–1.97
(m, 2H, CH2), 2.24–2.33 (m, 5H, CH2, Ar‐CH3), 2.58 (m, 2H,
3
CH2), 4.13 (s, 1H, CH), 6.94 (s, 2H, NH2), 7.02 (d, JH,H
=
3
8.0 Hz, 2H, Ar‐H), 7.08 (d, JH,H = 8.0 Hz, 2H, Ar‐H). MS
(ESI + ion): m/z = 281.2. Anal. Cacld for C17H16N2O2: C,
72.84%; H, 5.75; N, 9.99. Found: C, 72.87; H, 5.79; N, 10.05.
[4] (a) Hatakeyama, S.; Ochi, N.; Mumata, H.; Takano, S. J
Chem Soc Chem Commun 1988, 54, 1202; (b) Gonzalez, R.; Martin,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet