A.H. Kategaonkar et al. / European Journal of Medicinal Chemistry 45 (2010) 3142e3146
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with water and brine. The solvent was removed under reduced
4.9. 2-Chloro-8-methyl-3-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)
pressure to afford crude product 3, which was purified by column
quinoline (4d)
chromatography on silica gel by hexane:EtOAc (8:2) as an eluent.
1H NMR (300 MHz, DMSO-d6,
d
ppm): 2.31 (s, 3H, CH3), 5.87 (s,
2H, AreCH2), 7.14e7.64 (m, 8H, AreH), 8.34 (s, 1H, AreH), 8.51 (s,
4.4. 3-(Azidomethyl)-2-chloro-6-methylquinoline (3a)
1H, triazoleeH); 13C NMR (75 MHz, DMSO-d6,
d
ppm): 21.3 (CH3),
51.9 (AreCetriazole), 1119.7, 122.3, 124.6, 126.5, 127.3, 127.8, 128.2,
129.4, 129.8, 130.1, 130.7, 133.3, 137.6, 138.2, 146.7, 147.1, 152.4
(AreC); MS: m/z 335 (m þ 1), 337 (m þ 3); Elemental analysis:
C19H15ClN4 Calcd.: C: 68.16%; H: 4.52%; N: 16.73%; Found: C:
68.27%; H: 4.54%; N: 16.61%.
1H NMR (300 MHz, CDCl3,
1H, J ¼ 7 Hz, AreH), 7.68e7.78 (m, 2H, AreH), 7.98 (d, 1H, J ¼ 9 Hz,
AreH), 8.08 (s, 1H, AreH); 13C NMR (75 MHz, CDCl3,
ppm): 51.6
(AreCeN3), 126.6, 127.1, 127.2, 127.6, 127.8, 130.4, 137.1, 146.7, 149.0
(AreC); MS: m/z 219 (m þ 1), 221 (m þ 3); Elemental analysis:
C10H7ClN4 Calcd.: C: 54.93%; H: 3.23%; N: 25.62%; Found: C: 54.67%;
H: 3.40%; N: 25.74%.
d ppm): 4.59 (s, 2H, AreCH2), 7.53 (t,
d
4.10. 2-Chloro-6-methoxy-3-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)quinoline (4e)
4.5. General procedure for the synthesis of compounds (4aeh)
1H NMR (300 MHz, DMSO-d6,
2H, AreCH2), 7.27e7.94 (m, 8H, AreH), 8.29 (s, 1H, AreH), 8.63 (s,
1H, triazoleeH); 13C NMR (75 MHz, DMSO-d6,
ppm): 50.8
(AreCetriazole), 55.70 (OCH3), 106.4, 119.7, 120.2, 121.9, 122.0,
124.5, 125.3, 127.9, 128.9, 129.4, 130.6, 135.9, 139.7, 146.6, 148.8,
149.5, 161.7 (AreC); MS: m/z 351 (m þ 1), 353 (m þ 3); Elemental
analysis: C19H15ClN4O Calcd.: C: 65.05%; H: 4.31%; N: 15.97%;
Found: C: 65.24%; H: 4.24%; N: 15.75%.
d ppm): 3.76 (s, 3H, OCH3), 5.83 (s,
The azide compounds (3aeh) (1.3 equiv) and phenyl acetylene
(1 equiv) were dissolved in THF/H2O (9:1). To this solution,
CuSO4$5H2O (0.05 equiv) and sodium ascorbate (0.40 equiv) were
added. The reaction mixture was stirred for 11e12 h at room
temperature. After completion of reaction, reaction mixture was
poured on crushed ice. The solid obtained was extracted with EtOAc
(2 ꢂ 50 mL). The organic extract was washed with water and brine.
The solvent was removed under reduced pressure to afford crude
product (4aeh), which was purified by column chromatography on
silica gel by MeOH:CH2Cl2 (2:8) as an eluent to obtain compounds
(4aeh).
d
4.11. 2-Chloro-7-methoxy-3-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)quinoline (4f)
1H NMR (300 MHz, DMSO-d6,
2H, AreCH2), 7.32e7.83 (m, 8H, AreH), 8.09 (s, 1H, AreH), 8.76 (s,
1H, triazoleeH); 13C NMR (75 MHz, DMSO-d6,
ppm): 51.1
(AreCetriazole), 55.4 (OCH3), 105.7, 120.7, 121.1, 121.4, 122.6, 124.7,
125.9, 127.0, 128.7, 129.3, 130.9, 135.6, 140.7, 145.7,147.9, 149.6,159.8
(AreC); MS: m/z 351 (m þ 1), 353 (m þ 3); Elemental analysis:
C19H15ClN4O Calcd.: C: 65.05%; H: 4.31%; N: 15.97%; Found: C:
65.31%; H: 4.44%; N: 15.83%.
d ppm): 3.34 (s, 3H, OCH3), 5.84 (s,
4.6. 2-Chloro-3-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)quinoline
(4a)
d
1H NMR (300 MHz, DMSO-d6,
d ppm): 5.9 (s, 2H, AreCH2),
7.29e7.88 (m, 7H, AreH), 7.99 (d, 1H, J ¼ 9 Hz, AreH), 8.08 (d, 1H,
J ¼ 6 Hz, AreH), 8.39 (s, 1H, AreH), 8.67 (s, 1H, triazoleeH); 13C
NMR (75 MHz, DMSO-d6,
d ppm): 50.9 (AreCetriazole), 122.0,
125.2, 126.9, 127.3, 127.6, 127.8, 127.9, 128.2, 128.9, 130.6, 131.4,
133.4, 137.5, 139.8, 146.5, 146.7, 149.2 (AreC); MS: m/z 321 (m þ 1),
323 (m þ 3); Elemental analysis: C18H13ClN4 Calcd.: C: 67.40%; H:
4.08%; N: 17.47%; Found: C: 67.65%; H: 4.15%; N: 17.51%.
4.12. 2-Chloro-6-ethoxy-3-((4-phenyl-1H-1,2,3-triazol-1-yl)
methyl)quinoline (4g)
4.7. 2-Chloro-6-methyl-3-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)
quinoline (4b)
1H NMR (300 MHz, DMSO-d6,
d
ppm): 1.38 (t, 3H, J ¼ 6 Hz,
CH3eOCH2), 4.15 (q, 2H, J ¼ 6 Hz, OCH2), 5.89 (s, 2H, AreCH2),
7.31e7.89 (m, 8H, AreH), 8.11 (s, 1H, AreH), 8.69 (s,1H, triazoleeH);
1H NMR (300 MHz, DMSO-d6,
2H, AreCH2), 7.30e7.89 (m, 8H, AreH), 8.50 (s, 1H, AreH), 8.66 (s,
1H, triazoleeH); 13C NMR (75 MHz, DMSO-d6,
ppm): 21.0 (CH3),
d ppm): 2.48 (s, 3H, CH3), 5.89 (s,
13C NMR (75 MHz, DMSO-d6,
d ppm): 14.5 (CH3eCH2), 50.8
(AreCetriazole), 63.8 (CH2eCH3), 105.0, 106.6, 119.6, 120.4, 121.5,
122.1, 123.9, 125.2, 127.6, 127.9, 128.2, 128.9, 130.6, 135.8, 137.9,
142.5, 157.3 (AreC); MS: m/z 365 (m þ 1), 367 (m þ 3); Elemental
analysis: C20H17ClN4O Calcd.: C: 65.84%; H: 4.70%; N: 15.36%;
Found: C: 65.58%; H: 4.65%; N: 15.41%.
d
50.8 (AreCetriazole), 121.9, 122.8, 125.2, 126.8, 127.2, 127.3, 127.9,
128.9, 129.1, 129.6, 130.6, 133.4, 137.5, 139.1, 145.3, 146.5, 148.2
(AreC); MS: m/z 335 (m þ 1), 337 (m þ 3); Elemental analysis:
C19H15ClN4 Calcd.: C: 68.16%; H: 4.52%; N: 16.73%; Found: C:
68.24%; H: 4.41%; N: 16.65%.
4.13. 2-Chloro-8-ethyl-3-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)
4.8. 2-Chloro-7-methyl-3-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)
quinoline (4h)
quinoline (4c)
1H NMR (300 MHz, DMSO-d6,
d
ppm): 1.24 (t, 3H, J ¼ 6 Hz,
1H NMR (300 MHz, DMSO-d6,
2H, AreCH2), 7.26e7.83 (m, 8H, AreH), 8.57 (s, 1H, AreH), 8.71 (s,
1H, triazoleeH); 13C NMR (75 MHz, DMSO-d6,
ppm): 21.5 (CH3),
d
ppm): 2.25 (s, 3H, CH3), 5.84 (s,
CH3eCH2), 3.10 (q, 2H, J ¼ 6 Hz, CH3eCH2), 5.88 (s, 2H, AreCH2),
7.27e7.86 (m, 8H, AreH), 8.33 (s, 1H, AreH), 8.65 (s, 1H, tri-
d
azoleeH); 13C NMR (75 MHz, DMSO-d6,
d ppm): 15.0 (CH3eCH2),
51.7 (AreCetriazole), 120.7, 122.6, 124.2, 126.7, 127.1, 127.3, 127.9,
129.0, 129.1, 129.7, 130.3, 133.4, 137.5, 138.6, 146.0, 146.4, 150.1
(AreC); MS: m/z 335 (m þ 1), 337 (m þ 3); Elemental analysis:
C19H15ClN4 Calcd.: C: 68.16%; H: 4.52%; N: 16.73%; Found: C:
68.32%; H: 4.61%; N: 16.61%.
23.7 (CH2eCH3) 50.9 (AreCetriazole), 106.1, 120.4, 121.8, 122.0,
125.3, 126.1, 127.1, 127.7, 127.9, 128.9, 129.8, 130.6, 140.3, 141.2, 145.2,
146.6, 148.3 (AreC); MS: m/z 349 (m þ 1), 351 (m þ 3); Elemental
analysis: C20H17ClN4 Calcd.: C: 68.86%; H: 4.91%; N: 16.06%; Found:
C: 68.71%; H: 4.84%; N: 16.18%.