13
1
2937, 1771, 1394, 723 cm-1; H NMR (400 MHz, CDCl3) δH 9.64
3.4.31. 7-(1,3-Dioxoisoindolin-2-yl)-3-(4-isopropylphenyl)-N-
ACCEPTED MANUSCRIPT
(1H, br. s), 8.78 (1H, d, J = 3.2 Hz), 8.65 (1H, t, J = 4.5 Hz), 8.15
(1H, d, J = 7.7 Hz), 7.81 (2H, dd, J1 = 5.2, J2 = 3.1 Hz), 7.70 (2H,
dd, J1 = 5.4, J2 = 3.1 Hz), 7.49 (2H, d, J = 4.6 Hz), 7.46 (1H, dd, J1 =
8.3, J2 = 4.2 Hz), 7.39 (1H, d, J = 1.4 Hz), 7.32 (1H, d, J = 8.2 Hz),
7.13 (1H, dd, J1 = 8.2, J2 = 1.5 Hz), 3.67 (2H, t, J = 7.3 Hz), 3.36–
3.29 (1H, m), 2.87 (1H, dd, J1 = 14.8, J2 = 6.4 Hz), 2.80 (1H, dd, J1 =
14.8, J2 = 8.3 Hz), 1.92-1.82 (1H, m), 1.78-1.65 (2H, m), 1.60-1.52
(1H, m); 13C NMR (CDCl3, 101 MHz): δC 169.2, 168.3, 148.1, 143.9,
138.2, 136.3, 134.1, 133.9, 132.7, 132.0, 130.6, 130.6, 129.4, 127.9,
127.3, 127.2, 123.2, 121.6, 121.6, 116.5, 45.1, 41.6, 37.7, 33.2, 26.5;
HRMS (ESI) calcd for C29H24Cl2N3O3 [M+H]+ 532.1195 found
532.1177.
(quinolin-8-yl)heptanamide (11d): The compound 11d was
obtained after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a green color viscous liquid (55 mg,
70%); Rf (40% EtOAc/hexane) = 0.7; IR (DCM): 2933, 1711, 1525,
1326, 736 cm-1; H NMR (400 MHz, CDCl3) δH 9.69 (1H, br. s),
1
8.77 (1H, d, J = 4.0 Hz), 8.74 (1H, d, J = 7.2 Hz), 8.14 (1H, d, J =
8.2 Hz), 7.81 (2H, dd, J1 = 5.0, J2 = 3.2 Hz), 7.69 (2H, dd, J1 = 5.1,
J2 = 3.2 Hz), 7.53-7.47 (2H, m), 7.43 (1H, dd, J1 = 8.2, J2 = 4.2 Hz),
7.20 (2H, d, J = 7.8 Hz), 7.12 (2H, d, J = 7.8 Hz), 3.62 (2H, t, J = 7.2
Hz), 3.32-3.25 (1H, m), 2.85-2.78 (3H, m), 1.89-1.82 (1H, m), 1.78-
1.70 (2H, m), 1.65-1.56 (1H, m), 1.35-1.31 (1H, m), 1.26-1.24 (1H,
m), 1.17 (6H, d, J = 6.9 Hz); 13C NMR (CDCl3, 101 MHz): δC 170.4,
168.4, 148.0, 146.8, 141.2, 138.3, 136.3, 134.4, 133.8, 132.1, 127.9,
127.4, 127.3, 126.6, 123.1, 121.5, 121.3, 116.4, 45.7, 42.0, 37.8,
35.7, 33.6, 28.4, 24.7, 24.0, 23.9; HRMS (ESI) calcd for C33H34N3O3
[M+H]+ 520.2600, found 520.2623.
3.4.28. 3-(6-Chloropyridin-3-yl)-7-(1,3-dioxoisoindolin-2-yl)-N-
(quinolin-8-yl)heptanamide (11a): The compound 11a was
obtained after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a colourless solid (50 mg, 65%); Rf (40%
o
EtOAc/hexane) = 0.4; mp: 92-94 C; IR (DCM): 2936, 1708, 1524,
3.4.32. Methyl 4-(7-(1,3-dioxoisoindolin-2-yl)-1-oxo-1-(quinolin-
8-ylamino)heptan-3-yl)benzoate (11e): The compound 11e was
obtained after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a yellow color viscous liquid (58 mg,
72%); Rf (40% EtOAc/hexane) = 0.3; IR (DCM): 2939, 1712, 1525,
1396, 721 cm-1; H NMR (400 MHz, CDCl3) δH 9.69 (1H, br. s),
1
8.78 (1H, d, J = 3.8 Hz), 8.67 (1H, t, J = 4.4 Hz), 8.33 (1H, s), 8.15
(1H, d, J = 8.2 Hz), 7.82 (2H, dd, J1 = 5.0, J2 = 3.2 Hz), 7.70 (2H,
dd, J1 = 5.2, J2 = 3.3 Hz), 7.59 (1H, dd, J1 = 8.2, J2 = 1.9 Hz), 7.53-
7.49 (2H, m), 7.45 (1H, dd, J1 = 8.2, J2 = 4.2 Hz), 7.23 (1H, d, J =
8.2 Hz), 3.64 (2H, t, J = 7.2 Hz), 3.37-3.32 (1H, m), 2.92 (1H, dd, J1
= 15.0, J2 = 6.6 Hz), 2.80 (1H, dd, J1 = 14.9, J2 = 8.2 Hz), 1.92-1.83
(1H, m), 1.81-1.70 (2H, m), 1.68-1.61 (1H, m), 1.36-1.29 (1H, m),
1.25-1.21 (1H, m); 13C NMR (CDCl3, 101 MHz): δC 169.1, 168.3,
149.6, 149.2, 148.2, 138.2, 138.2, 138.0, 136.4, 134.0, 133.9, 132.0,
127.9, 127.3, 124.2, 123.2, 121.7, 121.7, 116.5, 44.8, 39.2, 37.5,
35.2, 28.2, 24.4; HRMS (ESI) calcd for C29H26ClN4O3 [M+H]+
513.1693, found 513.1667.
1282, 735 cm-1; H NMR (400 MHz, CDCl3) δH 9.67 (1H, br. s),
1
8.76 (1H, d, J = 3.8 Hz), 8.69 (1H, dd, J1 = 6.9, J2 = 2.0 Hz), 8.14
(1H, d, J = 8.2 Hz), 7.93 (2H, d, J = 8.0 Hz), 7.81 (2H, dd, J1 = 5.2,
J2 = 3.1 Hz), 7.69 (2H, dd, J1 = 5.3, J2 = 3.2 Hz), 7.52-7.47 (2H, m),
7.44 (1H, dd, J1 = 8.2, J2 = 4.2 Hz), 7.36 (2H, d, J = 8.0 Hz), 3.88
(3H, s), 3.62 (2H, t, J = 7.2 Hz), 3.43-3.36 (1H, m), 2.93-2.81 (2H,
m), 1.92-1.85 (1H, m), 1.82-1.74 (2H, m), 1.66-1.59 (1H, m), 1.34-
1.29 (1H, m), 1.24-1.17 (1H, m); 13C NMR (CDCl3, 101 MHz): δC
169.7, 168.3, 166.9, 149.4, 148.1, 138.2, 136.3, 134.2, 133.8, 132.0,
130.0, 128.4, 127.8, 127.6, 127.3, 123.1, 121.6, 121.5, 116.5, 51.9,
45.2, 42.4, 37.6, 35.4, 28.3, 24.5; HRMS (ESI) calcd for C32H30N3O5
[M+H]+ 536.2185, found 536.2204.
3.4.29.
3-(4-Chlorophenyl)-7-(1,3-dioxoisoindolin-2-yl)-N-
(quinolin-8-yl)heptanamide (11b): The compound 11b was
obtained after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a green color viscous liquid (50 mg,
65%); Rf (40% EtOAc/hexane) = 0.5; IR (DCM): 2938, 1712, 1526,
3.4.33.
3-(4-Chlorophenyl)-8-(1,3-dioxoisoindolin-2-yl)-N-
(quinolin-8-yl)octanamide (12a): The compound 12a was obtained
after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a yellow color viscous liquid (64 mg,
61%); Rf (40% EtOAc/hexane) = 0.5; IR (DCM): 3351, 2933, 1709,
1326, 720 cm-1; H NMR (400 MHz, CDCl3) δH 9.65 (1H, br. s),
1
8.77 (1H, d, J = 4.1 Hz), 8.70 (1H, dd, J1 = 6.6, J2 = 1.4 Hz), 8.14
(1H, dd, J1 = 8.2, J2 = 0.2 Hz), 7.82 (2H, dd, J1 = 5.0, J2 = 3.3 Hz),
7.70 (2H, dd, J1 = 5.9, J2 = 3.2 Hz), 7.53-7.47 (2H, m), 7.44 (1H, dd,
J1 = 8.2, J2 = 4.2 Hz), 7.21 (4H, s), 3.62 (2H, t, J = 7.2 Hz), 3.33-3.26
(1H, m), 2.89-2.77 (2H, m), 1.88-1.81 (1H, m), 1.75-1.68 (2H, m),
1.66-1.59 (1H, m), 1.32-1.20 (2H, m); 13C NMR (CDCl3, 101 MHz):
δC 169.8, 168.4, 148.1, 142.3, 138.2, 136.3, 134.3, 133.9, 132.1,
132.1, 128.9, 128.7, 127.9, 127.3, 123.1, 121.6, 121.5, 116.5, 45.5,
41.8, 37.7, 35.5, 28.3, 24.5; HRMS (ESI) calcd for C30H27ClN3O3
[M+H]+ 512.1741, found 512.1765.
1531, 721 cm-1; H NMR (400 MHz, CDCl3) δH 9.65 (1H, br. s),
1
8.75 (1H, dd, J1 = 4.1, J2 = 1.2 Hz), 8.70 (1H, dd, J1 = 6.8, J2 = 2.0
Hz), 8.13 (1H, dd, J1 = 8.2, J2 = 1.0 Hz), 7.81 (2H, dd, J1 = 5.3, J2 =
3.1 Hz), 7.68 (2H, dd, J1 = 5.3, J2 = 3.1 Hz), 7.51–7.46 (2H, m), 7.43
(1H, dd, J1 = 8.2, J2 = 4.2 Hz), 7.25-7.20 (4H, m), 3.62 (2H, t, J =
7.2 Hz), 3.31-3.24 (1H, m), 2.87-2.75 (2H, m), 1.83-1.76 (1H, m),
1.71-1.58 (3H, m), 1.38-1.18 (4H, m); 13C NMR (CDCl3, 101 MHz):
δC 169.9, 168.4, 148.1, 142.6, 138.1, 136.4, 134.2, 133.8, 132.1,
132.0, 128.9, 128.7, 127.9, 127.3, 123.1, 121.6, 121.5, 116.5, 45.7,
42.0, 37.9, 36.0, 28.4, 27.0, 26.8; HRMS (ESI) calculated for
C31H29ClN3O3 [M+H]+ 526.1897 found 526.1876.
3.4.30.
7-(1,3-Dioxoisoindolin-2-yl)-N-(quinolin-8-yl)-3-(4-
(trifluoromethyl)phenyl)heptanamide (11c): The compound 11c
was obtained after purification by column chromatography on silica
gel (EtOAc:hexane = 40:60) as a yellow color viscous liquid (55 mg,
67%); Rf (40% EtOAc/hexane) = 0.5; IR (DCM): 2936, 1710, 1524,
3.4.34.
8-(1,3-Dioxoisoindolin-2-yl)-3-(4-methoxyphenyl)-N-
(quinolin-8-yl)octanamide (12b): The compound 12b was obtained
after purification by column chromatography on silica gel
(EtOAc:hexane = 40:60) as a green color viscous liquid (53 mg,
68%); Rf (40% EtOAc/hexane) = 0.5; IR (DCM): 2930, 1708, 1523,
1326, 720 cm-1; H NMR (400 MHz, CDCl3) δH 9.66 (1H, br. s),
1
8.76 (1H, d, J = 2.8 Hz), 8.70 (1H, dd, J1 = 6.4, J2 = 2.2 Hz), 8.14
(1H, d, J = 7.1 Hz), 7.81 (2H, dd, J1 = 5.4, J2 = 3.1 Hz), 7.70 (2H,
dd, J1 = 5.3, J2 = 3.1 Hz), 7.51-7.48 (4H, m), 7.45 (1H, dd, J1 = 8.2,
J2 = 4.2 Hz), 7.40 (2H, d, J = 8.0 Hz), 3.63 (2H, t, J = 6.9 Hz), 3.41-
3.38 (1H, m), 2.93-2.81 (2H, m), 1.93-1.84 (1H, m), 1.82-1.75 (2H,
m), 1.67-1.58 (1H, m), 1.31-1.30 (1H, m), 1.25-1.20 (1H, m); 13C
NMR (CDCl3, 101 MHz): δC 169.6, 168.4, 148.1, 138.2, 136.3,
134.2, 133.9, 132.0, 128.7 (q, JC-F = 32.2 Hz ), 127.9, 127.9, 127.3,
125.5 (q, JC-F = 3.6 Hz ), 124.2 (q, JC-F = 271 Hz ), 123.1, 122.8,
121.6, 121.6, 116.5, 45.2, 42.2, 37.6, 35.4, 28.2, 24.5; HRMS (ESI)
calcd for C31H27F3N3O3 [M+H]+ 546.2005, found 546.2027.
1246, 720 cm-1; H NMR (400 MHz, CDCl3) δH 9.66 (1H, br. s),
1
8.77 (1H, d, J = 4.1 Hz), 8.72 (1H, d, J = 7.0 Hz), 8.14 (1H, d, J =
8.2 Hz), 7.83 (2H, dd, J1 = 5.1, J2 = 3.1 Hz), 7.70 (2H, dd, J1 = 5.2,
J2 = 3.2 Hz), 7.53–7.47 (2H, m), 7.44 (1H, dd, J1 = 8.3, J2 = 4.3 Hz),
7.20 (2H, d, J = 8.4 Hz), 6.82 (2H, d, J = 8.4 Hz), 3.75 (3H, s), 3.63
(2H, t, J = 7.3 Hz), 3.28-3.21 (1H, m), 2.86-2.76 (2H, m), 1.82-1.76
(1H, m), 1.63-1.58 (3H, m), 1.40-1.32 (3H, m), 1.24-1.18 (1H, m);
13C NMR (CDCl3, 101 MHz): δC 170.4, 168.4, 158.1, 148.0, 138.3,
136.2, 136.1, 134.4, 133.8, 132.2, 128.4, 127.9, 127.4, 123.1, 121.5,
121.3, 116.4, 114.0, 55.2, 46.1, 41.8, 38.0, 36.2, 28.5, 27.0, 26.9;
HRMS (ESI) calculated for C32H32N3O4 [M+H]+ 522.2393 found
522.2418.