JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
977
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
phenyl)-2,3,4-trimethoxybenzamide (1)
Procedure B in CHCl3 (free of ethanol), starting from aniline 27
and 2,3,4-trimethoxybenzoic acid.
Free base: chromatographic eluent: CH2Cl2/MeOH/NH4OH
97:3:0.3. Yield: 15.1%.
(OCH3); 55.93 (OCH3); 55.89 (OCH3); 55.59 (OCH3); 55.30 (CH2);
50.85 (CH2); 33.11 (CH2); 28.16 (CH2) ppm. ESI-HRMS (m/z) calcu-
lated for [M þ H]þ ion species C28H33N2O5¼ 477.2384,
found 477.2379.
Hydrochloride: mp 233–235 ꢀC.
1H NMR (400 MHz, CDCl3) d: 9.92 (s, 1H, NH); 7.98 (d, J ¼ 8.8 Hz,
1H, CH arom.); 7.60 (d, J ¼ 8.4 Hz, 2H, CH arom.); 7.23 (d, J ¼ 8.4 Hz,
2H, CH arom.); 6.82 (d, J ¼ 8.8 Hz, 1H, CH arom.); 6.60 (s, 1H, CH
arom.); 6.53 (s, 1H, CH arom.); 4.05 (s, 3H, OCH3); 3.92 (s, 3H,
OCH3); 3.90 (s, 3H, OCH3); 3.84 (s, 3H, OCH3); 3.83 (s, 3H, OCH3);
3.69 (s, 2H, NCH2Ar); 2.96–2.89 (m, 2H, CH2); 2.88–2.75 (m, 6H,
CH2) ppm. 13 C NMR (100 MHz, CDCl3) d: 162.71 (C¼O); 156.78 (C);
152.14 (C); 147.66 (C); 147.32 (C); 136.69 (C); 135.84 (C); 129.26 (CH
arom.); 126.96 (CH arom.); 125.97 (C); 125.91 (C); 120.33 (CH
arom.); 119.00 (C); 111.38 (CH arom.); 109.49 (CH arom.); 107.89
(CH arom.); 61.97 (OCH3); 61.05 (OCH3); 59.93 (CH2); 56.10 (OCH3);
55.95 (OCH3); 55.91 (OCH3); 55.46 (CH2); 50.91 (CH2); 33.24 (CH2);
28.35 (CH2) ppm. ESI-HRMS (m/z) calculated for [M þ H]þ ion spe-
cies C29H35N2O6¼ 507.2490, found 507.2492.
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
phenyl)-2,6-dimethoxybenzamide (4)
Procedure B in CHCl3 (free of ethanol), starting from aniline 27
and 2,6-dimethoxybenzoic acid.
Free base: chromatographic eluent: CH2Cl2/MeOH 95:5.
Yield: 75.0%.
1H NMR (400 MHz, CDCl3) d: 7.53 (d, J ¼ 8.4 Hz, 2H, CH arom.);
7.50 (s, 1H, NH); 7.24 (t, J ¼ 8.4 Hz, 1H, CH arom.); 7.15 (d,
J ¼ 8.4 Hz, 2H, CH arom.); 6.55 (s, 1H, CH arom.); 6.53 (d, J ¼ 8.4 Hz,
2H, CH arom.); 6.48 (s, 1H, CH arom.); 3.79 (s, 3H, OCH3); 3.78 (s,
3H, OCH3); 3.76 (s, 6H, OCH3); 3.63 (s, 2H, NCH2Ar); 2.90–2.70 (m,
8H, CH2) ppm. 13C NMR (100 MHz, CDCl3) d: 163.65 (C¼O); 157.55
(C); 147.64 (C); 147.31 (C); 136.58 (C); 135.85 (C); 131.03 (CH
arom.); 129.13 (CH arom.); 125.91 (C); 119.82 (CH arom.); 116.00
(C); 111.39 (CH arom.); 109.52 (CH arom.); 104.11 (CH arom.); 59.92
(CH2); 56.02 (OCH3); 55.94 (OCH3); 55.90 (OCH3); 55.42 (CH2); 50.90
(CH2); 33.17 (CH2); 28.34 (CH2) ppm. ESI-HRMS (m/z) calculated for
[M þ H]þ ion species C28H33N2O5¼ 477.2384, found 477.2384.
Hydrochloride: mp 212–214 ꢀC.
Hydrochloride: mp 208–211 ꢀC.
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
phenyl)-2-methoxybenzamide (2)
Procedure A in an. CH2Cl2, starting from aniline 27 and 2-methox-
ybenzoic acid.
Free base: chromatographic eluent: CH2Cl2/MeOH/NH4OH
97:3:0.3. Yield: 88.9%.
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
phenyl)-2,3-dimethoxybenzamide (5)
Procedure B in CHCl3 (free of ethanol), starting from aniline 27
and 2,3-dimethoxybenzoic acid.
Free base: chromatographic eluent: CH2Cl2/MeOH/NH4OH
97:3:0.3. Yield: 65.6%.
1H NMR (400 MHz, CDCl3) d: 9.71 (s, 1H, NH); 8.22 (d, J ¼ 8.0 Hz,
1H, CH arom.); 7.56 (d, J ¼ 8.4 Hz, 2H, CH arom.); 7.41 (t, J ¼ 8.0 Hz,
1H, CH arom.); 7.18 (d, J ¼ 8.4 Hz, 2H, CH arom.); 7.06 (t, J ¼ 8.0 Hz,
1H, CH arom.); 6.95 (d, J ¼ 8.0 Hz, 1H, CH arom.); 6.55 (s, 1H, CH
arom.); 6.49 (s, 1H, CH arom.); 3.96 (s, 3H, OCH3); 3.79 (s, 3H,
OCH3); 3.78 (s, 3H, OCH3); 3.60 (s, 2H, NCH2Ar); 2.90–2.67 (m, 8H,
CH2) ppm. 13C NMR (100 MHz, CDCl3) d: 163.13 (C¼O); 157.19 (C);
147.59 (C); 147.27 (C); 136.50 (C); 136.09 (C); 133.16 (CH arom.);
132.39 (CH arom.); 129.17 (CH arom.); 126.29 (C); 126.06 (C);
121.83 (C); 121.59 (CH arom.); 120.58 (CH arom.); 111.57 (CH
arom.); 111.44 (CH arom.); 109.56 (CH arom.); 60.03 (CH2); 56.21
(OCH3); 55.95 (OCH3); 55.91 (OCH3); 55.56 (CH2); 50.96 (CH2); 33.33
(CH2); 28.53 (CH2) ppm. ESI-HRMS (m/z) calculated for [M þ H]þ ion
species C27H31N2O4¼ 447.2278, found 447.2279.
1H NMR (400 MHz, CDCl3) d: 9.93 (s, 1H, NH); 7.73 (dd, J ¼ 8.0,
1.6 Hz, 1H, CH arom.); 7.58 (d, J ¼ 8.4 Hz, 2H, CH arom.); 7.20 (d,
J ¼ 8.4 Hz, 2H, CH arom.); 7.15 (t, J ¼ 8.0 Hz, 1H, CH arom.); 7.03
(dd, J ¼ 8.0, 1.6 Hz, 1H, CH arom.); 6.56 (s, 1H, CH arom.); 6.50 (s,
1H, CH arom.); 3.93 (s, 3H, OCH3); 3.87 (s, 3H, OCH3); 3.80 (s, 3H,
OCH3); 3.79 (s, 3H, OCH3); 3.62 (s, 2H, NCH2Ar); 2.90–2.84 (m, 2H,
CH2); 2.83–2.69 (m, 6H, CH2) ppm. 13C NMR (100 MHz, CDCl3) d:
162.90 (C¼O); 152.61 (C); 147.57 (C); 147.25 (C); 147.20 (C); 136.51
(C); 136.28 (C); 129.29 (CH arom.); 126.93 (C); 126.40 (C); 126.10
(C); 124.74 (CH arom.); 122.93 (CH arom.); 120.28 (CH arom.);
115.70 (CH arom.); 111.40 (CH arom.); 109.52 (CH arom.); 61.65
(OCH3); 60.13 (CH2); 56.14 (OCH3); 55.94 (OCH3); 55.91 (OCH3);
55.64 (CH2); 51.00 (CH2); 33.40 (CH2); 28.62 (CH2) ppm. ESI-HRMS
(m/z) calculated for [M þ H]þ ion species C28H33N2O5¼ 477.2384,
found 477.2375.
Hydrochloride: mp 226–228 ꢀC.
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
phenyl)-2,4-dimethoxybenzamide (3)
Procedure B in CHCl3 (free of ethanol), starting from aniline 27
and 2,4-dimethoxybenzoic acid.
Hydrochloride: mp 230–233 ꢀC.
Free base: chromatographic eluent: CH2Cl2/MeOH/NH4OH
97:3:0.3. Yield: 54.7%.
1H NMR (400 MHz, CDCl3) d: 9.69 (s, 1H, NH); 8.26 (d, J ¼ 8.8 Hz,
N-(4–(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-
1H, CH arom.); 7.60 (d, J ¼ 8.4 Hz, 2H, CH arom.); 7.23 (d, J ¼ 8.4 Hz, phenyl)-1-naphthamide (6)
2H, CH arom.); 6.66 (dd, J ¼ 8.8 Hz, 2.2 Hz, 1H, CH arom.); 6.62 (s, Procedure B in CHCl3 (free of ethanol), starting from aniline 27
1H, CH arom.); 6.55 (s, 1H, CH arom.); 6.54 (d, J ¼ 2.2 Hz, 1H, CH and 1-naphthoic acid.
arom.); 4.03 (s, 3H, OCH3); 3.88 (s, 3H, OCH3); 3.86 (s, 3H, OCH3);
Free base: chromatographic eluent: CH2Cl2/MeOH/NH4OH
3.85 (s, 3H, OCH3); 3.73 (s, 2H, NCH2Ar); 3.00–2.94 (m, 2H, CH2); 97:3:0.3. Yield: 53.6%.
1H NMR (400 MHz, CDCl3) d: 8.29–8.27 (m, 1H, CH arom.); 7.95
2.93–2.77 (m, 6H, CH2) ppm. 13C NMR (100 MHz, CDCl3) d: 163.70
(C¼O); 163.04 (C); 158.51 (C); 147.66 (C); 147.31 (C); 136.78 (C);
135.43 (C); 134.16 (CH arom.); 129.18 (CH arom.); 125.71 (C);
(s, 1H, NH); 7.87 (d, J ¼ 7.6 Hz, 1H, CH arom.); 7.84–7.81 (m, 1H, CH
arom.); 7.62 (d, J ¼ 7.6 Hz, 1H, CH arom.); 7.56 (d, J ¼ 8.4 Hz, 2H, CH
120.57 (CH arom.); 114.67 (C); 111.27 (CH arom.); 109.38 (CH arom.); 7.51–7.46 (m, 2H, CH arom.); 7.38 (t, J ¼ 7.6 Hz, 1H, CH
arom.); 105.65 (CH arom.); 98.74 (CH arom.); 59.80 (CH2); 56.20 arom.); 7.19 (d, J ¼ 8.4 Hz, 2H, CH arom.); 6.56 (s, 1H, CH arom.);