Arch. Pharm. Chem. Life Sci. 2009, 342, 100–112
Synthesis and in-vitro Antimycobacterial Evaluation
109
1-Cyclopropyl-1,4-dihydro-8-methyl-6-nitro-7-(4-
(piperidin-1-yl)piperidin-1-yl)-4-oxoquinoline-3-carboxylic
1-tert-Butyl-7-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-
yl)-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-3-
acid 9h
carboxylic acid 11i
Yield: 80%; m.p.: 199–2018C; 1H NMR (DMSO-d6) d ppm: 0.28–
0.48 (m, 4H, cyclopropyl), 1.35 (m, 1H, cyclopropyl), 1.5–1.6 (m,
10H, 5 CH2), 2.2 (t, J = 8.3 Hz, 4H, 2 CH2), 2.38 (s, 3H, CH3), 2.7 (m,
1H, CH), 2.8 (t, J = 8.3 Hz, 4H, 2 CH2), 7.32 (s, 1H, C5-H), 8.2 (s, 1H,
C2-H), 14.6 (s, 1H, COOH);13C NMR (DMSO-d6) d ppm: 177.5, 166.3,
151.1, 148.1, 146.2, 126.5, 121.9, 117.5, 109.3, 99.3, 58.2, 52.4,
47.2, 36.0, 28.2, 26.3, 25.8, 6.4, 5.6; Anal. Calcd. for C24H30N4O5: C,
63.42; H, 6.65; N, 12.33; Found: C, 63.01; H, 6.70; N, 12.47.
Yield: 85%; m.p.: A2808C; 1H NMR (DMSO-d6) d ppm: 1.74 (s, 9H, t-
butyl), 2.0 (t, J = 13.5 Hz, 4H, 3,5-CH2 of piperidine), 2.38 (s, 3H,
CH3), 2.7 (t, J = 13.5 Hz, 4H, 2,6-CH2 of piperidine), 7.1–7.18 (m,
4H, Ar-H), 7.82 (s, 1H, C5-H), 8.88 (s, 1H, C2-H), 10.0 (bs, 1H, OH),
14.6 (s, 1H, COOH);13C NMR (DMSO-d6) d ppm: 177.5, 166.3, 151.1,
148.1, 146.2, 138.2, 131.5, 129.6, 129.1, 126.5, 121.9, 117.5,
109.3, 99.3, 74.4, 65.0, 42.9, 38.2, 28.5, 6.4, ; Anal. Calcd. for
C26H28ClN3O6: C, 60.75; H, 5.49; N, 8.18; Found: C, 60.69; H, 5.99;
N, 8.14.
1-(2,4-Difluorophenyl)-1,4-dihydro-8-methyl-6-nitro-7-(4-
(piperidin-1-yl)piperidin-1-yl)-4-oxoquinoline-3-carboxylic
acid 10h
7-(4-(6-Chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-
yl)piperidin-1-yl)-1-cyclopropyl-1,4-dihydro-8-methyl-6-
Yield: 95%; m.p.: >2808C; 1H NMR (DMSO-d6) d ppm: 1.5–1.6 (m,
10H, 5 CH2), 2.2 (t, J = 8.3 Hz, 4H, 2 CH2), 2.38 (s, 3H, CH3), 2.7 (m,
1H, CH), 2.8 (t, J = 8.3 Hz, 4H, 2 CH2), 6.42–6.75 (m, 3H, Ar-H), 8.2
(s, 1H, C2-H), 14.6 (s, 1H, COOH); 13C NMR (DMSO-d6) d ppm: 177.5,
166.3, 152.4, 149.4, 147.7, 146.3, 136.3, 126.6, 123.1, 120.7,
116.4, 109.3, 104.9, 58.2, 52.4, 47.2, 28.2, 26.3, 25.8, 6.4; Anal.
Calcd. for C27H28F2N4O5: C, 61.59; H, 5.36; N, 10.64; Found: C,
61.05; H, 5.40; N, 10.49.
nitro-4-oxoquinoline-3-carboxylic acid 9j
Yield: 82%; m.p.: 246–2488C; 1H NMR (DMSO-d6) d ppm: 0.28–
0.48 (m, 4H, cyclopropyl), 1.35 (m, 1H, cyclopropyl), 1.6–2.4 (m,
8H, 4 CH2 of piperidine), 2.38 (s, 3H, CH3), 4.1 (bm, 1H, CH of
piperidine), 6.8–7.7 (m, 3H, Ar-H), 7.88 (s, 1H, C5-H), 8.3 (s, 1H, C2-
H), 10.8 (s, 1H, NH), 14.6 (s, 1H, COOH);13C NMR (DMSO-d6) d ppm:
177.5, 166.3, 151.7, 151.1, 148.1, 146.2, 131.3, 130.2, 126.5,
124.8, 123.2, 122.2, 121.9, 117.5, 109.3, 99.3, 50.5, 46.5, 36.0,
26.8, 6.4, 5.6; Anal. Calcd. for C26H24ClN5O6: C, 58.05; H, 4.50; N,
13.02; Found: C, 58.26; H, 4.61; N, 13.11.
1-tert-Butyl-1,4-dihydro-8-methyl-6-nitro-7-(4-(piperidin-
1-yl)piperidin-1-yl)-4-oxoquinoline-3-carboxylic acid 11h
1
Yield: 75%; m.p.: 204–2068C; H NMR (DMSO-d6) d ppm: 1.78 (s,
7-(4-(6-Chloro-1,2-dihydro-2-oxobenzo[d]imidazol-3-
yl)piperidin-1-yl)-1-(2,4-difluorophenyl)-1,4-dihydro-8-
9H, t-butyl), 1.5-1.6 (m, 10H, 5 CH2), 2.2 (t, J = 8.3 Hz, 4H, 2 CH2),
2.38 (s, 3H, CH3), 2.7 (m, 1H, CH), 2.8 (t, J = 8.3 Hz, 4H, 2 CH2), 7.32
(s, 1H, C5-H), 8.2 (s, 1H, C2-H), 14.6 (s, 1H, COOH); 13C NMR (DMSO-
d6) d ppm: 177.5, 166.3, 151.1, 148.1, 146.2, 126.5, 121.9, 117.5,
109.3, 99.3, 65.0, 58.2, 52.4, 47.2, 28.5, 28.2, 25.8, 26.3, 6.4; Anal.
Calcd. for C25H34N4O5: C, 63.81; H, 7.28; N, 11.91; Found: C, 64.01;
H, 7.80; N, 11.47.
methyl-6-nitro-4-oxoquinoline-3-carboxylic acid 10j
Yield: 91%; m.p.: 204–2068C; 1H NMR (DMSO-d6) d ppm: 1.6–2.4
(m, 8H, 4 CH2 of piperidine), 2.38 (s, 3H, CH3), 4.1 (bm, 1H, CH of
piperidine), 6.5–7.7 (m, 6H, Ar-H), 8.3 (s, 1H, C2-H), 10.8 (s, 1H,
NH), 14.6 (s, 1H, COOH); 13C NMR (DMSO-d6) d ppm: 177.5, 166.3,
152.4, 151.7, 149.4, 147.7, 146.3, 136.3, 131.3, 130.2, 126.6,
124.8, 123.1, 122.2, 120.7, 116.4, 109.3, 104.9, 50.5, 46.5, 26.8,
6.4; Anal. Calcd. C29H22ClF2N5O6: C, 57.10; H, 3.64; N, 11.48;
Found: C, 57.61; H, 3.66; N, 11.43.
7-(4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl)-1-
cyclopropyl-1,4-dihydro-8-methyl-6-nitro-4-oxoquinoline-
3-carboxylic acid 9i
1
Yield: 86%; m.p.: 232–2348C; H NMR (DMSO-d6) d ppm: 0.28–
1-tert-Butyl-7-(4-(6-chloro-1,2-dihydro-2-
oxobenzo[d]imidazol-3-yl)piperidin-1-yl)-1,4-dihydro-8-
0.46 (m, 4H, cyclopropyl), 1.33 (m, 1H, cyclopropyl), 2.0 (t, J =
13.5 Hz, 4H, 3,5-CH2 of piperidine), 2.38 (s, 3H, CH3), 2.7 (t, J =
13.5 Hz, 4H, 2,6-CH2 of piperidine), 7.1–7.18 (m, 4H, Ar-H), 7.82
(s, 1H, C5-H), 8.88 (s, 1H, C2-H), 10.0 (bs, 1H, OH), 14.6 (s, 1H,
COOH); 13C NMR (DMSO-d6) d ppm: 177.5, 166.3, 151.1, 148.1,
146.2, 138.2, 131.5, 129.6, 129.1, 126.5, 121.9, 117.5, 109.3, 99.3,
74.4, 42.9, 38.2, 36.0, 6.4, 5.6; Anal. Calcd. for C25H24ClN3O6: C,
60.30; H, 4.86; N, 8.44; Found C, 60.60; H, 4.99; N, 8.54.
methyl-6-nitro-4-oxoquinoline-3-carboxylic acid 11j
Yield: 89%; m.p.: 211–2138C; 1H NMR (DMSO-d6) d ppm: 1.75 (s,
9H, t-butyl), 1.6–2.4 (m, 8H, 4 CH2 of piperidine), 2.38 (s, 3H,
CH3), 4.1 (bm, 1H, CH of piperidine), 6.8–7.7 (m, 3H, Ar-H), 7.88
(s, 1H, C5-H), 8.3 (s, 1H, C2-H), 10.8 (s, 1H, NH), 14.6 (s, 1H, COOH);
13C NMR (DMSO-d6) d ppm: 177.5, 166.3, 151.7, 151.1, 148.1,
146.2, 131.3, 130.2, 126.5, 124.8, 123.2, 122.2, 121.9, 117.5,
109.3, 99.3, 65.0, 50.5, 46.5, 28.5, 26.8, 6.4; Anal. Calcd. for
C27H28ClN5O6: C, 58.54; H, 5.09; N, 12.64; Found: C, 58.26; H, 5.01;
N, 12.61.
7-(4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl)-1-(2,4-
difluorophenyl)-1,4-dihydro-8-methyl-6-nitro-4-
oxoquinoline-3-carboxylic acid 10i
Yield: 92%; m.p.: 273–2758C; 1H NMR (DMSO-d6) d ppm: 2.0 (t, J =
13.5 Hz, 4H, 3,5-CH2 of piperidine), 2.38 (s, 3H, CH3), 2.7 (t, J =
13.5 Hz, 4H, 2,6-CH2 of piperidine), 6.45–7.18 (m, 7H, Ar-H), 8.88
(s, 1H, C2-H), 10.0 (bs, 1H, OH), 14.6 (s, 1H, COOH); 13C NMR
(DMSO-d6) d ppm: 177.5, 166.3, 152.4, 149.4, 147.7, 146.3, 138.2,
131.5, 136.3, 129.6, 129.1, 126.6, 123.1, 120.7, 116.4, 109.3,
104.9, 74.4, 42.9, 38.2, 6.4 ; Anal. Calcd. for C28H22ClF2N3O6: C,
59.01; H, 3.89; N, 7.37; Found: C, 59.01; H, 3.83; N, 7.31.
1-Cyclopropyl-7-(3-(diethylcarbamoyl)piperidin-1-yl)-1,4-
dihydro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylic acid
9k
Yield: 82%; m.p.: 268–2708C; 1H NMR (DMSO-d6) d ppm: 0.28–
0.48 (m, 4H, cyclopropyl), 1.35 (m, 1H, cyclopropyl), 1.2 (t, J =
7.1 Hz, 6H, 2-CH3 of ethyl), 1.78–2.7 (m, 9H, H of piperidine), 2.38
(s, 3H, CH3), 3.24 (q, J = 7.15 Hz, 4H, 2-CH2 of ethyl), 7.8 (s, 1H, C5-
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