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B. Vaitilingam et al. / Bioorg. Med. Chem. 12 (2004) 4179–4188
1H, J ¼ 8:2 Hz); EIMS m=z 351 (Mþ). Anal. Calcd for
C23H29NO2 (351.5): C, 78.59; H, 8.32; N, 3.99. Found:
C, 78.75; H, 8.03; N, 4.11.
5.9. General method for the synthesis of methyl/ethyl 2-(2-
substituted/2,8-disubstituted-4-quinolyl)acetates (14a–j)
These analogues were synthesized from methyl 2-(4-
quinolyl)acetate (13a) or ethyl 2-(4-quinolyl)acetate
(13b) using procedure reported above for methyl ring-
substituted-2-quinolinecarboxylate (3a–g).
5.7.5. Methyl 2-(1-adamantyl)-4-quinolinecarboxylate
(11e). Yield: 28%; mp 107–109 ꢁC; IR (KBr)
1729 cmꢀ1 1H NMR (CDCl3) d 1.33–1.56 (m, 15H),
;
4.04 (s, 3H), 7.57 (m, 1H), 7.71 (m, 1H), 7.81 (s, 1H),
8.12 (d, 1H, J ¼ 8:4 Hz), 8.66 (d, 1H, J ¼ 8:4 Hz); EIMS
m=z 322 (M + 1). Anal. Calcd for C21H23NO2 (321.4): C,
78.47; H, 7.21; N, 4.36. Found: C, 78.77; H, 7.51; N,
4.35.
5.9.1. Methyl 2-(2-cyclopentyl-4-quinolyl)acetate (14a).
Yield: 39%; oil; IR (neat) 1729 cmꢀ1; 1H NMR (CDCl3)
1.76–1.93 (m, 8H), 2.81 (m, 1H), 3.72 (s, 3H), 4.03 (s,
2H), 7.15 (s, 1H), 7.51 (m, 1H), 7.73 (m, 1H), 7.91 (d,
1H, J ¼ 8:3 Hz), 8.05 (d, 1H, J ¼ 8:3 Hz); ESIMS m=z
270 (M + 1). Anal. Calcd for C17H19NO2 (269.3): C,
75.81; H, 7.11; N, 5.20. Found: C, 75.74; H, 7.33; N,
5.29.
5.7.6. Methyl 2,8-di(1-adamantyl)-4-quinolinecarboxylate
(11f). Yield: 17%; mp 92–93 ꢁC; IR (KBr) 1709 cmꢀ1; 1H
NMR (CDCl3) d 1.46–1.67 (m, 30H), 3.93 (s, 3H), 7.57
(m, 1H), 7.78 (m, 1H), 7.83 (s, 1H), 8.31 (d, 1H,
J ¼ 8:1 Hz); EIMS m=z 456 (M + 1). Anal. Calcd for
C31H37NO2 (455.6): C, 81.72; H, 8.19; N, 3.07. Found:
C, 81.88; H, 8.09; N, 3.18.
5.10. Methyl 2-(2,8-dicyclopentyl-4-quinolyl)acetate
(14b)
Yield: 12%; oil; IR (neat) 1730 cmꢀ1; NMR (CDCl3) d
1.67–1.87 (m, 16H), 2.73 (m, 2H), 4.01 (s, 2H), 3.92 (s,
3H), 6.93 (s, 1H), 7.52 (m, 1H), 7.60 (d, 1H, J ¼ 7:9 Hz),
7.81 (d, 1H, J ¼ 8:2 Hz); APCIMS m=z 338 (M + 1).
Anal. Calcd for C22H27NO2 (337.5): C, 78.30; H, 8.06;
N, 4.15. Found: C, 78.16; H, 7.88; N, 4.37.
5.8. General method for the synthesis of ring-substituted-
4-quinolinecarboxylic acid hydrochlorides (12a–c)
These analogues were synthesized from methyl 2-cyclo-
pentyl-4-quinolinecarboxylate (11a), methyl 2-cyclo-
hexyl-4-quinolinecarboxylate (11c) and methyl 2-(1-
adamantyl)-4-quinolinecarboxylate (11e) using proce-
dure reported above for ring-substituted-2-quinoline-
carboxylic acid hydrochlorides (4a–b).
5.10.1. Methyl 2-(2-cyclohexyl-4-quinolyl)acetate (14c).
Yield: 42%; oil; IR (neat) 1729 cmꢀ1; 1H NMR (CDCl3)
1.55–1.70 (m, 10H), 2.88 (m, 1H), 3.72 (s, 3H), 4.08 (s,
2H), 7.17 (s, 1H), 7.54 (m, 1H), 7.70 (m, 1H), 7.89 (d,
1H, J ¼ 8:3 Hz), 8.01 (d, 1H, J ¼ 8:3 Hz); APCIMS m=z
284 (M + 1). Anal. Calcd for C18H21NO2 (283.4): C,
76.29; H, 7.47; N, 4.94. Found: C, 76.22; H, 7.81; N,
4.91.
5.8.1. 2-Cyclopentyl-4-quinolinecarboxylic acid hydro-
chloride (12a). Yield 94%; mp 97–98 ꢁC; IR (KBr)
3405, 2925, 1712, 1638 cmꢀ1 1H NMR (CD3OD) d
;
1.71–1.91 (m, 8H), 2.69 (m, 1H), 8.00 (m, 1H), 8.19 (m,
1H), 8.31 (d, 1H, J ¼ 8:7 Hz), 8.39 (s, 1H), 8.91 (d, 1H,
J ¼ 8:6 Hz); ESIMS m=z 242 (M + 1). Anal. Calcd for
C15H16ClNO2 (277.8): C, 64.87; H, 5.81; N, 5.04. Found:
C, 64.95; H, 5.93; N, 5.17.
5.10.2. Methyl 2-(2,8-dicyclohexyl-4-quinolyl)acetate
(14d). Yield: 12%; oil; IR (neat) 1730 cmꢀ1; NMR
(CDCl3) d 1.65–1.80 (m, 20H), 2.91 (m, 2H), 3.75 (s,
3H), 4.01 (s, 2H), 6.91 (s, 1H), 7.48 (m, 1H), 7.64 (d, 1H,
J ¼ 7:9 Hz), 7.79 (d, 1H, J ¼ 8:2 Hz); ESIMS m=z 366
(M + 1). Anal. Calcd for C24H31NO2 (365.5): C, 78.86;
H, 8.55; N, 3.83. Found: C, 78.88; H, 8.54; N, 3.97.
5.8.2. 2-Cyclohexyl-4-quinolinecarboxylic acid hydrochlo-
ride (12b). Yield 94%; mp 102–104 ꢁC; IR (KBr) 3425,
2925, 1682, 1537 cmꢀ1; 1H NMR (CD3OD) d 1.21–1.31
(m, 10H), 3.32 (m, 1H), 7.96 (m, 1H), 8.15 (m, 1H), 8.26
(d, 1H, J ¼ 8:3 Hz), 8.33 (s, 1H), 8.90 (d, 1H,
J ¼ 8:2 Hz); EIMS m=z 255 (Mþ). Anal. Calcd for
C16H18ClNO2 (291.8): C, 65.86; H, 6.22; N, 4.80. Found:
C, 65.72; H, 6.43; N, 4.81.
5.10.3. Methyl 2-[(1-adamantyl)-4-quinolyl]acetate (14e).
;
1H
Yield: 35%; mp 52–54 ꢁC; IR (KBr) 1733 cmꢀ1
NMR (CDCl3) 1.70–1.90 (m, 15H), 3.70 (s, 3H), 4.06 (s,
2H), 6.91 (s, 1H), 7.51 (m, 1H), 7.67 (m, 1H), 7.92 (d,
1H, J ¼ 8:3 Hz), 8.10 (d, 1H, J ¼ 8:3 Hz); EIMS m=z
335 (Mþ). Anal. Calcd for C22H25NO2 (335.4): C, 78.77;
H, 7.51; N, 4.18. Found: C, 78.69; H, 7.34; N, 4.41.
5.8.3. 2-(1-Adamantyl)-4-quinolinecarboxylic acid hydro-
chloride (12c). Yield 97%; mp 112–114 ꢁC; IR (KBr)
3422, 2921, 1680, 1525 cmꢀ1 1H NMR (CD3OD) d
;
1.41–1.52 (m, 15H), 7.89 (m, 1H), 8.11 (m, 1H), 8.30 (d,
1H, J ¼ 8:3 Hz), 8.38 (s, 1H), 8.83 (d, 1H, J ¼ 8:3 Hz);
EIMS m=z 307 (Mþ). Anal. Calcd for C20H22ClNO2
(343.9): C, 69.86; H, 6.45; N, 4.07. Found: C, 69.68; H,
6.57; N, 4.03.
5.10.4. Ethyl 2-(2-cyclopentyl-4-quinolyl)acetate (14f).
Yield: 45%; oil; IR (neat) 1733cmꢀ1
(CDCl3) 1.23 (t, 3H, J ¼ 6:9 Hz), 1.60–1.90 (m, 8H),
2.88 (m, 1H), 4.03 (s, 2H), 4.15 (m, 2H), 7.21 (s, 1H),
7.50 (m, 1H), 7.67 (m, 1H), 7.94 (d, 1H, J ¼ 8:4 Hz),
;
1H NMR