General procedure for the synthesis of substituted 2-chloro-N-phenylacetamide (3a-o)
Chloroacetyl chloride 2 (1.68 g, 1.5 mmol) was added dropwise to the ice cooled stirring solution of substituted anilines (1a-o) (1.5 mmol) in DCM, in the presence of triethyl amine (4.5 mmol, 0.46 g) as base. Reaction was further stirred at rt for 2 to 3 h, progress of the reaction was monitored with TLC. After completion of reaction, DMC layer was washed with distilled water, dried over sodium sulphate and evaporated on rotary evaporator to yield the intermediates (3a-o).
General procedure for the synthesis of substituted 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenyl acetamide (5a-o)
Substituted 2-chloro-N-phenylacetamide (intermediates 3a-o, 1 mmol) was added to the stirring reaction mass of 4, in acetonitrile in the presence of potassium carbonate as base. Reaction mass was further allowed to reflux for 5 to 7 h, progress of the reaction was monitored by the TLC (Scheme 1). After completion of reaction, solvent acetonitrile was evaporated on rotary evaporator; water was added to the reaction mixture and extracted twice with equal volume (25 ml) of ethyl acetate. Combined ethyl acetate layer was washed with brine water, dried over sodium sulphate and evaporated on rotary evaporator to afford the final compounds 5a-o.
Synthesis of 2-chloro-1-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)ethanone (6)
Chloroacetyl chloride 2 (2.24 g, 20 mmol) was added dropwise to the ice cooled stirring solution of starting material 4 (4.6 g, 20 mmol) in DCM, in a round-bottom flask using triethyl amine (7.0 ml, 50 mmol,) as base (Scheme 2). Reaction mixture was further stirred at rt for 2.5 h until completion as per TLC. After completion of reaction, DMC layer was washed with distilled water once and then with brine water and dried over sodium sulphate and finally evaporated on rotary evaporator to afford the titled compounds.
General procedure for the synthesis of substituted 1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(phenylamino) ethanone using Microwave irradiation (8a-o)
2-methoxyaniline (7a) (0.12 g, 1 mmol) and chloro intermediate 6 (0.27 g, 1 mmol) was taken in microwave reaction vial in presence of potassium carbonate as base (0.347 g, 2.5 mmol) (Scheme 2). The microwave oven model Cata RI was programmed to 300 W at 100 °C for 2 to 4.5 min. The reaction was monitored using TLC. After completion of reaction, ice water was added to the reaction mixture which resulted the precipitation of the product. The solid product was filtered off and washed with excess cold water and dried to afford product 8a. Similar apporoach was followed for the synthesis of rest of the compounds (8b-o).
The spectral characterization of the synthesized derivatives
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylacetamide (5a)
Yield 73 %; white solid, MF: C19H22N2O3; MW: 326.16; MP: 151–154 °C; IR (KBr, ν, cm−1): 3288, 3001, 2821, 2775, 1693, 1517, 1423, 1228, 1139, 1105; 1H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 7.59 (dd, J = 8.6, 1.1 Hz, 2H), 7.39 – 7.31 (m, 2H), 7.14 (d, J = 7.4 Hz, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.88 (d, J = 12.2 Hz, 6H), 3.77 (s, 2H), 3.34 (s, 2H), 2.92 (s, 4H); MS: m/z 327 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-o-tolylacetamide (5b)
Yield 76 %; white solid, MF: C20H24N2O3; MW: 340.18; MP: 137–139 °C; IR (KBr, ν, cm−1): 3294, 2975, 2914, 2829, 1670, 1490, 1251, 1226, 1139, 1013; 1H NMR (400 MHz, CDCl3) δ 9.33 (s, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.25 (s, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.06 (td, J = 7.5, 1.2 Hz, 1H), 6.66 (s, 1H), 6.54 (s, 1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.79 (s, 2H), 3.38 (s, 2H), 2.95 (d, J = 3.8 Hz, 4H), 2.20 (s, 3H); MS: m/z 341 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-m-tolylacetamide (5c)
Yield 78 %; white solid, MF: C20H24N2O3; MW: 340.18; MP: 131–133 °C; IR (KBr, ν, cm−1): 3286, 3010, 2949, 2833, 1683, 1519, 1489, 1220, 1143, 1024; 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 1H), 7.40 (d, J = 11.8 Hz, 2H), 7.23 (t, J = 7.7 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.88 (d, J = 12.3 Hz, 6H), 3.74 (d, J = 17.9 Hz, 2H), 3.33 (s, 2H), 2.98 – 2.80 (m, 4H), 2.36 (s, 3H); MS: m/z 341 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-p-tolylacetamide (5d)
Yield 81 %; white solid, MF: C20H24N2O3; MW: 340.18; MP: 151–153 °C; IR (KBr, ν, cm−1): 3267, 2943, 2827, 2779, 1685, 1517, 1462, 1253, 1196; 1H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 7.51 – 7.42 (m, 2H), 7.15 (d, J = 8.2 Hz, 2H), 6.67 (s, 1H), 6.55 (s, 1H), 3.88 (d, J = 12.1 Hz, 6H), 3.76 (s, 2H), 3.32 (s, 2H), 2.91 (d, J = 3.1 Hz, 3H), 2.33 (s, 3H); MS: m/z 341 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-methoxyphenyl)acetamide (5e)
Yield 76 %; white solid, MF: C20H24N2O4; MW: 356.18; MP: 139–141 °C; IR (KBr, ν, cm−1): 3277, 2922, 2829, 1685, 1597, 1523, 1465, 1255, 1139, 1005; 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 1H), 7.42 (d, J = 11.7 Hz, 2H), 7.24 (t, J = 7.8 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.66 (s, 1H), 6.54 (s, 1H), 3.88 (d, J = 12.3 Hz, 6H), 3.82 (s, 3H), 3.72 (d, J = 17.9 Hz, 2H), 3.32 (s, 2H), 2.96 – 2.78 (m, 4H); MS: m/z 357 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(4-methoxyphenyl)acetamide (5f)
Yield 84 %; white solid, MF: C20H24N2O4; MW: 356.18; MP: 153–155 °C; IR (KBr, ν, cm−1): 3317, 2957, 2920, 2821, 1688, 1615, 1517, 1467, 1253, 1134, 1103; 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 7.51 (s, 1H), 7.48 (s, 1H), 6.89 (d, J = 2.2 Hz, 1H), 6.87 (d, J = 2.2 Hz, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.81 (s, 3H), 3.76 (s, 2H), 3.32 (s, 2H), 2.92 (s, 4H); MS: m/z 357 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(4-fluorophenyl)acetamide (5g)
Yield 71 %; white solid, MF: C20H24N2O4; MW: 344.15; MP: 153–155 °C; IR (KBr, ν, cm−1): 3302, 3070, 2991, 2816, 1687, 1612, 1508, 1469, 1228, 1136, 1101; 1H NMR (400 MHz, CDCl3) δ 9.20 (s, 1H), 7.65 – 7.49 (m, 2H), 7.08 – 7.00 (m, 2H), 6.67 (s, 1H), 6.55 (s, 1H), 3.88 (d, J = 11.6 Hz, 6H), 3.76 (s, 2H), 3.33 (s, 2H), 2.92 (s, 4H), 1.60 (s, 2H); MS: m/z 345 (M + 1).
N-(2-chlorophenyl)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetamide (5h)
Yield 64 %; white solid, MF: C19H21ClN2O3; MW: 360.12; MP: 109–111 °C; IR (KBr, ν, cm−1): 3298, 2993, 2889, 2833, 1701, 1519, 1436, 1230, 1139, 1103; 1H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 8.48 (dd, J = 8.3, 1.5 Hz, 1H), 7.37 (dd, J = 8.0, 1.4 Hz, 1H), 7.32 (dd, J = 7.5, 1.0 Hz, 1H), 7.10 – 7.01 (m, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.81 (s, 2H), 3.38 (s, 2H), 2.94 (s, 4H); MS: m/z 361 (M + 1).
N-(3-chlorophenyl)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetamide (5i)
Yield 69 %; white solid, MF: C19H21ClN2O3; MW: 360.12; MP: 176–178 °C; IR (KBr, ν, cm−1): 3228, 3001, 2821, 2752, 1663, 1517, 1423, 1228, 1138, 1005; 1H NMR (400 MHz, CDCl3) δ 9.27 (s, 1H), 7.69 (t, J = 2.0 Hz, 1H), 7.45 (ddd, J = 8.2, 2.0, 0.9 Hz, 1H), 7.10 (ddd, J = 8.0, 2.0, 1.0 Hz, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.89 (d, J = 12.4 Hz, 6H), 3.76 (s, 2H), 3.33 (s, 2H), 2.92 (d, J = 3.5 Hz, 4H); MS: m/z 361 (M + 1).
N-(4-chlorophenyl)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)acetamide (5j)
Yield 74 %; white solid, MF: C19H21ClN2O3; MW: 360.12; MP: 177–179 °C; IR (KBr, ν, cm−1): 3269, 2941, 2900, 2825, 2785, 1680, 1517, 1492, 1396, 1253, 1220, 1141, 1105; 1H NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 7.56 – 7.53 (m, 2H), 7.31 (s, 2H), 6.67 (s, 1H), 6.55 (s, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.76 (s, 2H), 3.33 (s, 2H), 2.92 (s, 4H); MS: m/z 361 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(4-nitrophenyl)acetamide (5k)
Yield 67 %; light yellow solid, MF: C19H21N3O5; MW: 371.15; MP: 192–194 °C; IR (KBr, ν, cm−1): 3273, 2933, 2829, 1703, 1504, 1336, 1226; 1H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 8.23 (d, J = 9.2 Hz, 2H), 7.77 (d, J = 9.2 Hz, 2H), 6.68 (s, 1H), 6.55 (s, 1H), 3.89 (d, J = 14.3 Hz, 6H), 3.78 (s, 2H), 3.38 (s, 2H), 2.94 (s, 4H); MS: m/z 372 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-(trifluoromethyl)phenyl) acetamide (5l)
Yield 68 %; white solid, MF: C20H21F3N2O3; MW: 394.15; MP: 176–178 °C; IR (KBr, ν, cm−1): 3302, 3070, 2991, 2816, 1687, 1612, 1508, 1469, 1228, 1136, 1101; 1H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 7.90 (s, 1H), 7.77 (d, J = 7.9 Hz, 1H), 7.45 (t, J = 7.9 Hz, 1H), 7.36 (d, J = 7.7 Hz, 1H), 6.68 (s, 1H), 6.58 (s, 1H), 3.90 (s, 3H), 3.86 (d, J = 9.9 Hz, 5H), 3.73 (d, J = 14.1 Hz, 1H), 3.46 (d, J = 6.7 Hz, 1H), 2.91 (d, J = 5.3 Hz, 2H), 2.88 – 2.76 (m, 2H); MS: m/z 395 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(2,6-dimethylphenyl)acetamide (5m)
Yield 77 %; white solid, MF: C21H26N2O3; MW: 354.19; MP: 155–157 °C; IR (KBr, ν, cm−1): 3315, 2956, 2920, 2821, 1691, 1610, 1517, 1467, 1253, 1132, 1103; 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 7.10 (d, J = 1.6 Hz, 3H), 6.66 (s, 1H), 6.56 (s, 1H), 3.88 (d, J = 3.5 Hz, 6H), 3.83 (s, 2H), 3.40 (s, 2H), 2.99 (d, J = 5.0 Hz, 2H), 2.95 (d, J = 5.2 Hz, 2H), 2.26 (s, 6H); MS: m/z 355 (M + 1).
2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3,4-dimethylphenyl)acetamide (5n)
Yield 75 %; white solid, MF: C21H26N2O3; MW: 354.19; MP: 158–160 °C; IR (KBr, ν, cm−1): 3332, 3045, 2997, 2831, 2773, 1693, 1519, 1489, 1225, 1230, 1138, 1101; 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 7.35 (s, 2H), 7.09 (d, J = 7.9 Hz, 1H), 6.67 (s, 1H), 6.55 (s, 1H), 3.90 (s, 3H), 3.87 (s, 3H), 3.76 (s, 2H), 3.33 (s, 2H), 2.92 (s, 4H), 2.25 (d, J = 9.1 Hz, 6H); MS: m/z 355 (M + 1).
N-(5-chloro-2-methylphenyl)-2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl) acetamide (5o)
Yield 68 %; white solid, MF: C20H23ClN2O3; MW: 374.14; MP: 117–119 °C; IR (KBr, ν, cm−1): 3277, 3016, 2937, 2900, 2829, 1701, 1514, 1445, 1259, 1228, 1190, 1136; 1H NMR (400 MHz, CDCl3) δ 9.44 (s, 1H), 8.02 (dd, J = 6.7, 2.7 Hz, 1H), 7.22 – 7.12 (m, 2H), 6.67 (s, 1H), 6.54 (s, 1H), 3.88 (d, J = 11.5 Hz, 6H), 3.80 (s, 2H), 3.38 (s, 2H), 3.04 – 2.86 (m, 4H), 2.25 (s, 3H); MS: m/z 375 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2-methoxyphenylamino) ethanone (8a)
Yield 73 %; white solid, MF: C20H24N2O4; MW: 356.17; MP: 91–92 °C; IR (KBr, ν, cm−1): 3419, 3062, 2991, 2833, 1656, 1604, 1514, 1415, 1263, 1234, 1118; 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J = 9.4, 4.5 Hz, 1H), 7.12 (s, 1H), 6.69 – 6.64 (m, 2H), 6.64 – 6.53 (m, 2H), 4.76 (s, 1H), 4.58 (s, 1H), 4.06 (s, 1H), 3.93 (t, J = 5.9 Hz, 1H), 3.91 – 3.83 (m, 7H), 3.76 (s, 3H), 3.70 (t, J = 5.9 Hz, 1H), 2.92 (t, J = 5.7 Hz, 1H), 2.86 (t, J = 5.7 Hz, 1H); MS: m/z 257 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(3-methoxyphenylamino) ethanone (8b)
Yield 79 %; white solid, MF: C20H24N2O4; MW: 356.17; MP: 118–119 °C; IR (KBr, ν, cm−1): 3361, 2999, 2953, 2833, 1643, 1606, 1517, 1421, 1224, 1163, 1112; 1H NMR (400 MHz, CDCl3) δ 7.13 (t, J = 8.1 Hz, 1H), 6.74 – 6.60 (m, 2H), 6.32 (dt, J = 5.8, 3.0 Hz, 2H), 6.22 (d, J = 1.7 Hz, 1H), 4.74 (s, 1H), 4.56 (s, 1H), 3.97 (s, 2H), 3.94 – 3.86 (m, 7H), 3.81 (s, 3H), 3.68 (t, J = 5.9 Hz, 1H), 2.89 (t, J = 5.9 Hz, 1H), 2.83 (t, J = 5.9 Hz, 1H); MS: m/z 257 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(4-methoxyphenylamino) ethanone (8c)
Yield 83 %; white solid, MF: C20H24N2O4; MW: 356.17; MP: 116–117 °C; IR (KBr, ν, cm−1): 3356, 2951, 2833, 1643, 1517, 1365, 1253, 1211, 1114, 821; 1H NMR (400 MHz, CDCl3) δ 6.83 (d, J = 8.5 Hz, 2H), 6.72 – 6.58 (m, 4H), 4.74 (s, 1H), 4.57 (s, 1H), 3.96 (s, 2H), 3.93 – 3.86 (m, 7H), 3.78 (s, 3H), 3.69 (t, J = 5.9 Hz, 1H), 2.89 (t, J = 5.6 Hz, 1H), 2.83 (t, J = 5.7 Hz, 1H); MS: m/z 257 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(3-fluorophenylamino) ethanone (8d)
Yield 76 %; white solid, MF: C19H21FN2O3; MW: 344.15; MP: 144–145 °C; IR (KBr, ν, cm−1): 3361, 2981, 2910, 2833, 1656, 1612, 1517 1433, 1365, 1253, 1222, 1112; 1H NMR (400 MHz, CDCl3) δ 7.19 – 7.08 (m, 1H), 6.69 – 6.65 (m, 2H), 6.49 – 6.38 (m, 2H), 6.34 (dq, J = 11.5, 2.3 Hz, 1H), 4.75 (s, 1H), 4.57 (s, 1H), 3.96 (d, J = 2.4 Hz, 2H), 3.93 – 3.88 (m, 7H), 3.69 (t, J = 5.9 Hz, 1H), 2.87 (dt, J = 25.9, 5.8 Hz, 2H); MS: m/z 345 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(4-fluorophenylamino) ethanone (8e)
Yield 81 %; white solid, MF: C19H21FN2O3; MW: 344.15; MP: 126–12 °C; IR (KBr, ν, cm−1): 3365, 2939, 1837, 1643, 1514, 1440, 1265, 1222, 1116; 1H NMR (400 MHz, CDCl3) δ 6.93 (t, J = 8.7 Hz, 2H), 6.69 – 6.64 (m, 2H), 6.61 (ddd, J = 8.9, 4.3, 2.1 Hz, 2H), 4.85 (s, 1H), 4.74 (s, 1H), 4.57 (s, 1H), 3.95 (s, 2H), 3.91 – 3.85 (m, 7H), 3.69 (t, J = 5.9 Hz, 1H), 2.90 (t, J = 5.8 Hz, 1H), 2.83 (t, J = 5.9 Hz, 1H); MS: m/z 345 (M + 1).
2-(2-chlorophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl) ethanone (8f)
Yield 68 %; white solid, MF: C19H21ClN2O3; MW: 360; MP: 104–105 °C; IR (KBr, ν, cm−1): 3379, 2999, 2933, 2835, 1665, 1517, 1485, 1415, 1257, 1228, 1209, 1111; 1H NMR (400 MHz, CDCl3) δ 7.31 (dd, J = 7.9, 1.4 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.68 (s, 2H), 6.66 – 6.58 (m, 2H), 4.76 (s, 1H), 4.59 (s, 1H), 4.03 (d, J = 1.9 Hz, 2H), 3.93 (s, 1H), 3.89 (d, J = 3.2 Hz, 6H), 3.70 (t, J = 5.9 Hz, 1H), 2.91 (t, J = 5.7 Hz, 1H), 2.85 (t, J = 5.9 Hz, 1H); MS: m/z 361 (M + 1).
2-(3-chlorophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (8g)
Yield 84 %; white solid, MF: C19H21ClN2O3; MW: 360; MP: 136–137 °C; IR (KBr, ν, cm−1): 3367, 3053, 2954, 2933, 2833, 1656, 1593, 1514, 1392, 1261, 1228, 1116; 1H NMR (400 MHz, CDCl3) δ 7.14 – 7.06 (m, 1H), 6.71 (dd, J = 7.9, 1.2 Hz, 1H), 6.67 (d, J = 3.2 Hz, 2H), 6.63 – 6.60 (m, 1H), 6.56 (dt, J = 8.2, 2.2 Hz, 1H), 4.73 (d, J = 15.0 Hz, 1H), 4.57 (s, 1H), 3.97 – 3.92 (m, 2H), 3.89 (dd, J = 8.1, 5.4 Hz, 7H), 3.68 (t, J = 5.9 Hz, 1H), 2.90 (t, J = 5.9 Hz, 1H), 2.84 (t, J = 5.8 Hz, 1H); MS: m/z 361 (M + 1).
2-(4-chlorophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl) ethanone (8h)
Yield 75 %; white solid, MF: C19H21ClN2O3; MW: 360; MP: 115–116 °C; IR (KBr, ν, cm−1): 3360, 2927, 2906, 2833, 1658, 1600, 1511, 1433, 1265, 1226, 1124; 1H NMR (400 MHz, CDCl3) δ 7.16 (d, J = 8.7 Hz, 2H), 6.69 – 6.63 (m, 2H), 6.59 (dd, J = 8.9, 2.3 Hz, 2H), 4.74 (s, 1H), 4.57 (s, 1H), 3.95 (d, J = 2.9 Hz, 2H), 3.92 – 3.87 (m, 7H), 3.68 (s, 1H), 2.90 (t, J = 5.9 Hz, 1H), 2.84 (s, 1H); MS: m/z 361 (M + 1).
2-(2-bromophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl) ethanone (8i)
Yield 68 %; white solid, MF: C19H21BrN2O3; MW: 404.07; MP: 109–110 °C; IR (KBr, ν, cm−1): 3379, 2999, 2931, 2837, 1649, 1517, 1433, 1442, 1257, 1228, 1207; 1H NMR (400 MHz, CDCl3) δ 7.50 (dd, J = 9.4, 4.5 Hz, 1H), 7.22 (s, 1H), 6.69 – 6.64 (m, 2H), 6.64 – 6.53 (m, 2H), 4.76 (s, 1H), 4.58 (s, 1H), 4.06 (s, 1H), 3.93 (t, J = 5.9 Hz, 1H), 3.91 – 3.83 (m, 7H), 3.70 (t, J = 5.9 Hz, 1H), 2.91 (t, J = 5.7 Hz, 1H), 2.85 (t, J = 5.7 Hz, 1H); MS: m/z 405 (M + 1).
2-(3-bromophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (8j)
Yield 75 %; white solid, MF: C19H21BrN2O3; MW: 404.07; MP: 123–124 °C; IR (KBr, ν, cm−1): 3369, 2954, 2931, 2833, 1649, 1591, 1514, 1485, 1433, 1259, 1228, 1112; 1H NMR (400 MHz, CDCl3) δ 7.06 (t, J = 8.0 Hz, 1H), 6.86 (dd, J = 7.8, 1.0 Hz, 1H), 6.77 (dd, J = 4.0, 2.0 Hz, 1H), 6.67 (d, J = 2.7 Hz, 2H), 6.61 (dd, J = 8.2, 2.3 Hz, 1H), 4.75 (s, 1H), 4.57 (s, 1H), 3.95 (d, J = 1.2 Hz, 2H), 3.92 (s, 2H), 3.91 – 3.88 (m, 5H), 3.69 (t, J = 5.9 Hz, 1H), 2.91 (t, J = 5.8 Hz, 1H), 2.84 (t, J = 5.9 Hz, 1H); MS: m/z 405 (M + 1).
2-(4-bromophenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (8k)
Yield 72 %; white solid, MF: C19H21BrN2O3; MW: 404.07; MP: 117–118 °C; IR (KBr, ν, cm−1): 3358, 2985, 2902, 2833, 1643, 1517, 1433, 1396, 1285, 1224, 1124; 1H NMR (400 MHz, CDCl3) δ 7.31 (s, 1H), 6.67 (d, J = 5.2 Hz, 2H), 6.64 – 6.45 (m, 3H), 5.02 (s, 1H), 4.74 (s, 1H), 4.57 (s, 1H), 3.94 (s, 2H), 3.91 – 3.87 (m, 7H), 3.68 (t, J = 5.8 Hz, 1H), 2.90 (t, J = 5.8 Hz, 1H), 2.84 (t, J = 6.0 Hz, 1H); MS: m/z 405 (M + 1).
4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethylamino)benzonitrile (8l)
Yield 68 %; white solid, MF: C20H21N3O3; MW: 351.16; MP: 146–147 °C; IR (KBr, ν, cm−1): 3358, 2985, 2902, 2833, 2208, 1643, 1517, 1433, 1396, 1285, 1224, 1124; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.5 Hz, 2H), 6.68 (d, J = 4.6 Hz, 2H), 6.65 – 6.62 (m, 2H), 5.60 (s, 1H), 4.75 (s, 1H), 4.57 (s, 1H), 4.00 (t, J = 4.0 Hz, 2H), 3.91 (s, 1H), 3.89 (t, J = 2.7 Hz, 6H), 3.68 (s, 1H), 2.91 (t, J = 5.7 Hz, 1H), 2.85 (t, J = 5.7 Hz, 1H); MS: m/z 352 (M + 1).
2-(3-acetylphenylamino)-1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone (8m)
Yield 66 %; white solid, MF: C21H24N2O4; MW: 368.17; MP: 111–112 °C; IR (KBr, ν, cm−1): 3365, 2937, 2835, 1672, 1643, 1598, 1517, 1359, 1315, 1259, 1224, 1116; 1H NMR (400 MHz, CDCl3) δ 7.36 – 7.30 (m, 2H), 7.22 – 7.20 (m, 1H), 6.94 – 6.90 (m, 1H), 6.68 (s, 2H), 4.75 (s, 1H), 4.60 (s, 1H), 4.03 (s, 2H), 3.94 (s, 1H), 3.90 – 3.88 (m, 6H), 3.71 (t, J = 5.9 Hz, 1H), 2.91 (t, J = 5.8 Hz, 1H), 2.84 (t, J = 5.9 Hz, 1H), 2.61 (s, 3H); MS: m/z 369 (M + 1).
(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(3(trifluoromethyl)phenylamino) ethanone (8n)
Yield 76 %; white solid, MF: C20H21F3N2O3; MW: 394.15; MP: 135–136 °C; IR (KBr, ν, cm−1): 3350, 2910, 2835, 1643, 1612, 1514, 1431, 1359, 1284, 1261, 1222, 1109; 1H NMR (400 MHz, CDCl3) δ 7.30 (s, 1H), 6.99 (d, J = 7.7 Hz, 1H), 6.84 (s, 2H), 6.68 (t, J = 3.1 Hz, 2H), 4.76 (s, 1H), 4.59 (s, 1H), 4.00 (s, 2H), 3.92 (s, 1H), 3.90 (d, J = 2.5 Hz, 6H), 3.71 (t, J = 5.9 Hz, 1H), 2.92 (t, J = 5.9 Hz, 1H), 2.85 (t, J = 5.8 Hz, 1H); MS: m/z 395 (M + 1).
1-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-(2,5-dimethylphenylamino) ethanone (8o)
Yield 75 %; white solid, MF: C21H26N2O3; MW: 354.19; MP: 140–141 °C; IR (KBr, ν, cm−1): 3402, 2995, 2833, 1643, 1517, 1415, 1255, 1232, 1207, 1112; 1H NMR (400 MHz, CDCl3) δ 6.67 (d, J = 4.6 Hz, 2H), 6.44 (s, 1H), 6.35 (s, 2H), 4.74 (s, 1H), 4.58 (s, 1H), 3.98 (s, 2H), 3.91 (s, 1H), 3.89 (t, J = 4.3 Hz, 6H), 3.70 (t, J = 5.9 Hz, 1H), 2.90 (t, J = 5.9 Hz, 1H), 2.83 (t, J = 6.0 Hz, 1H), 2.28 (s, 6H); MS: m/z 355 (M + 1).