ACCEPTED MANUSCRIPT
(M+H). Anal. Calcd for (C16H18N4O4): C, 58.17; H, 5.49; N, 16.96. Found: C, 58.15; H, 5.52; N,
16.93.
5.1.9.3. Ethyl 6-ethoxy-4-methoxy-1-methyl-1H-[1,2,3]triazolo[4,5-h]quinoline-7-carboxylate
1
(22c). M.P.: 105-106 °C. Yield: 84%. H-NMR: (DMSO-d6) δ: 8.97 (s, 1H, H8), 7.16 (s, 1H, H5),
4.71 (s, 3H, CH3), 4.42 (q, 2H, CH2CH3), 4.27 (q, 2H, CH2CH3), 4.11 (s, 3H, CH3), 1.47 (t, 3H,
13
CH3CH2), 1.39 (t, 3H, CH3CH2). C-NMR: (DMSO-d6) δ: 164.60 (C), 161.34 (C), 149.74 (C),
148.39 (CH), 140.02 (C), 136.38 (C), 130.47 (C), 123.74 (C), 116.46 (C), 94.60 (CH), 71.82 (CH2),
61.48 (CH2), 56.01 (CH3), 37.57 (CH3), 15.33 (CH3), 13.96 (CH3). GC/MS: 331 (M+H). Anal.
Calcd for (C16H18N4O4): C, 58.17; H, 5.49; N, 16.96. Found: C, 58.16; H, 5.50; N, 16.94.
5.1.9.4. Ethyl 4-ethoxy-9-ethyl-3-methyl-6-oxo-6,9-dihydro-3H-[1,2,3]triazolo[4,5-h]quinoline-7-
1
carboxylate (31a). M.P.: 192-193 °C. Yield: 73%. H-NMR: (CDCl3) δ: 8.49 (s, 1H, H8), 7.88 (s,
1H, H5), 5.10 (q, 2H, N- CH2CH3), 4.56 (s, 3H, CH3), 4.28-4.48 (m, 4H, 2 CH2CH3), 1.41-1.67 (m,
9H, 3 CH3CH2). 13C-NMR: (DMSO-d6) δ: 174.32 (C), 164.09 (C), 146.20 (CH), 142.98 (C), 138.66
(C), 128.03 (C), 126.49 (C), 126.05 (C), 110.83 (C), 102.57 (CH), 64.31 (CH2), 61.40 (CH2), 51.86
(CH2), 36.22 (CH3), 14.41 (CH3), 14.32 (CH3), 14.26 (CH3). GC/MS: 344 (M+H). ). Anal. Calcd
for (C17H20N4O4): C, 59.29; H, 5.85; N, 16.27. Found: C, 59.31; H, 5.88; N, 16.26.
5.1.10. General procedure for the synthesis of alkoxy-methyl-6-oxo-6,9-dihydro-triazolo[4,5-
h]quinoline-7-carboxylic acid (23a-c, 32a). 0.5 g of the adequate alkoxy-methyl-6-oxo-6,9-
dihydro-triazolo[4,5-h]quinoline-7-carboxylate derivatives (22a-c or 31a) are dissolved in 22 ml of
2 M NaOH. The mixture is brought to 100 ° C for 2 hours under magnetic stirring. The basic, clear
solution is returned to room temperature and subsequently acidified with 2 M HCl; a very fine
gelatinous precipitate is formed which is filtered (albeit with difficulty) and dried, obtaining pure
carboxylic acid.
5.1.10.1.
9-ethyl-4-methoxy-3-methyl-6-oxo-6,9-dihydro-3H-[1,2,3]triazolo[4,5-h]quinoline-7-
carboxylic acid (23a). M.P.> 300 °C. Yield: 86%. 1H-NMR: (DMSO-d6) δ: 15.11 (s, 1H, OH), 9.08
(s, 1H, H8), 7.68 (s, 1H, H5), 5.25 (q, 2H, CH2-CH3), 4,54 (s, 3H, NCH3), 4.13 (s, 3H, OCH3), 1.50
13
(t, 3H, CH3-CH2). C-NMR: (DMSO-d6) δ: 175.77 (C), 165.95 (C), 147.27 (CH), 144.96 (C),
138.12 (C), 129.48 (C), 127.66 (C), 123.63 (C), 109.22 (C), 100.66 (CH), 59.87 (CH2), 56.77
(CH3), 52.63 (CH2), 37.39 (CH3), 15.73 (CH3). GC/MS: 303 (M+H). Anal. Calcd for (C14H14N4O4):
C, 55.63; H, 4.67; N, 18.53. Found: C, 55.60; H, 4.64; N, 18.54.
5.1.10.2.
9-ethyl-4-methoxy-2-methyl-6-oxo-6,9-dihydro-2H-[1,2,3]triazolo[4,5-h]quinoline-7-
1
carboxylic acid (23b). M.P.: 273-274 °C. Yield: 95%. H-NMR: (DMSO-d6) δ: 15.83 (s, 1H, OH),
9.03 (s, 1H, H8), 7.47 (s, 1H, H5), 5.05 (m, 2H, CH2CH3), 4.62 (s, 3H, OCH3), 4.08 (s, 3H, CH3),
13
1.47 (t, 3H, CH3CH2). C-NMR: (DMSO-d6) δ: 175.71 (C), 166.00 (C), 148.31 (C), 146.46 (CH),
142.27 (C), 140.14 (C), 127.56 (C), 125.03 (C), 111.10 (C), 99.05 (CH), 56.18 (CH3), 52.30 (CH2),
43.99 (CH3), 15.69 (CH3). GC/MS: 303 (M+H). Anal. Calcd for (C14H14N4O4): C, 55.63; H, 4.67;
N, 18.53. Found: C, 55.66; H, 4.70; N, 18.51.
5.1.10.3. 6-ethoxy-4-methoxy-1-methyl-1H-[1,2,3]triazolo[4,5-h]quinoline-7-carboxylic acid (23c).
M.P.: 194-195 °C. Yield: 76%. 1H-NMR: (DMSO-d6) δ: 8.98 (s, 1H, H8), 7.17 (s, 1H, H5), 4.71 (s,
13
3H, OCH3), 4.32 (q, 2H, CH2), 4.11 (s, 3H, CH3), 1.46 (t, 3H, CH3). C-NMR: (DMSO-d6) δ:
166.16 (C), 161.25 (C), 149.58 (C), 148.66 (CH), 139.90 (C), 136.19 (C), 130.45 (C), 123.78 (C),
117.25 (C), 94.58 (CH), 71.55 (CH2), 57.21 (CH3), 37.55 (CH3), 15.57 (CH3). GC/MS: 303 (M+H).
Anal. Calcd for (C14H14N4O4): C, 55.63; H, 4.67; N, 18.53. Found: C, 55.62; H, 4.68; N, 18.55.
5.1.10.4.
4-ethoxy-9-ethyl-3-methyl-6-oxo-6,9-dihydro-3H-[1,2,3]triazolo[4,5-h]quinoline-7-
carboxylic acid (32a). M.P.: 263-264 °C. Yield: 57%. 1H-NMR: (CDCl3) δ: 15.43 (s, 1H, OH), 8.75
(s, 1H, H8), 7.75 (s, 1H, H5), 5.21 (q, 2H, OCH2CH3), 4.40 (q, 2H, OCH2CH3), 1.60 (m, 6H, 2
CH3CH2). 13C-NMR: (DMSO-d6) δ: 175.29 (C), 166.37 (C), 149.09 (CH), 140.33 (C), 138.01 (C),
128.47 (C), 126.39 (C), 126.37 (C), 110.77 (C), 102.67 (CH), 64.11 (CH2), 51.32 (CH2), 35.41