9
7.39 (d, 1H, J = 8.2 Hz), 3.33 – 3.30 (m, 1H), 2.95 -2.82 (m, 2H),
20:80) to give the corresponding C-H arylated product (see the
respective Tables/Schemes for the specific entries).
ACCEPTED MANUSCRIPT
2.54 (s, 3H), 1.91 – 1.86 (m, 1H), 1.78 – 1.70 (m, 1H), 0.85 (t, 3H, J
= 7.3 Hz); 13C NMR (100 MHz, CDCl3): δ 197.8, 169.9, 149.9,
148.1, 138.2, 136.3, 135.6, 134.3, 128.7, 127.9, 127.9, 127.3, 121.6,
121.5, 116.4, 45.0, 44.3, 29.0, 26.6, 12.0; HRMS (ESI): MH+, found
347.1752 C22H23N2O2 requires 347.1760.
3.2.1. 3-(3-Fluorophenyl)-N-(quinolin-8-yl)butanamide (5c):
Following the general procedure, 5c was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a brown colour oil (126 mg, 81%); Rf = 0.5 (EtOAc:Hexane =
1
20:80); FTIR (DCM): 3351, 2967, 1691, 1589 and 1528 cm-1; H
3.2.6. 3-(4-Chlorophenyl)-N-(quinolin-8-yl)pentanamide (7c):
Following the general procedure, 7c was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
colourless thick liquid (80 mg, 78%); Rf = 0.5 (EtOAc:Hexane =
NMR (400 MHz, CDCl3): δ 9.75 (s, 1H), 8.80 – 8.77 (m, 2H), 8.16
(d, 1H, J = 8.2 Hz), 7.54 – 7.44 (m, 3H), 7.28 - 7.24 (m, 1H), 7.14 –
7.05 (m, 2H), 6.90 (t, 1H, J = 8.3 Hz), 3.54 – 3.51 (m, 1H), 2.92 -
2.87 (m, 1H), 2.82 – 2.76 (m, 1H), 1.43 (d, 3H J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3): δ 169.9, 163.1 (d, JC-F = 243 Hz), 148.6 (d, JC-F
= 6.9 Hz), 148.1, 138.3, 136.3, 134.3, 130 (d, JC-F = 8.1 Hz), 127.9,
20:80); FTIR (DCM): 3351, 2928, 1682, 1529 and 1485 cm-1; H
1
NMR (400 MHz, CDCl3): δ 9.67 (s, 1H), 8.78 (dd, 1H, J1 = 4.2 Hz,
J2 = 1.4 Hz), 8.73 (dd, 1H, J1 = 6.8 Hz, J2 = 2.0 Hz), 8.16 (dd, 1H, J1
= 8.3 Hz, J2 = 1.4 Hz), 7.54 – 7.44 (m, 3H), 7.27 (d, 2H, J = 7.3 Hz),
7.24 (d, 2H, J = 7.3 Hz), 3.24 – 3.20 (m, 1H), 2.92 – 2.78 (m, 2H),
1.90 – 1.84 (m, 1H), 1.73 – 1.69 (m, 1H), 0.85 (t, 3H, J = 7.3 Hz);
13C NMR (100 MHz, CDCl3): δ 170.1, 148.1, 142.5, 138.2, 136.3,
134.3, 132.0, 129.0, 128.7, 127.9, 127.4, 121.6, 121.5, 116.4, 45.4,
43.8, 29.1, 12.0; HRMS (ESI): MH+, found 339.1279 C20H20ClN2O
requires 339.1264.
127.4, 122.7 (d, JC-F = 2.5 Hz), 121.6, 121.5, 116.5, 113.7 (d, JC-F
=
21.1 Hz), 113.3 (d, JC-F = 20.8 Hz), 46.6, 36.6, 21.7; HRMS (ESI):
MH+, found 309.1393. C19H18FN2O requires 309.1403.
3.2.2.
3-(4-Ethylphenyl)-N-(quinolin-8-yl)butanamide
(5i):
Following the general procedure, 5i was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a colourless solid ( 117 mg, 74%); Rf = 0.5 (EtOAc:Hexane = 20:80);
mp 69 – 70 oC; FTIR (DCM): 3354, 2963, 1686, 1526 and 1484 cm-
3.2.7. 3-(3-Fluorophenyl)-N-(quinolin-8-yl)pentanamide (7d):
Following the general procedure, 7d was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a colourless semi liquid (87 mg, 90%); Rf = 0.5 (EtOAc:Hexane =
1
1; H NMR (400 MHz, CDCl3): δ 9.78 (s, 1H), 8.83 – 8.79 (m, 2H),
8.15 (d, 1H, J = 8.2 Hz), 7.56 – 7.49 (m, 2H), 7.45 (dd, 1H, J1 = 8.2
Hz, J2 = 4.2 Hz), 7.29 (d, 2H, J = 7.6 Hz), 7.19 (d, 2H, J = 7.6 Hz),
3.55 – 3.49 (m, 1H), 2.92 (dd, 1H, J1 = 14.4 Hz, J2 = 6.4 Hz), 2.79
(dd, 1H, J1 = 14.4 Hz, J2 = 8.4 Hz), 2.63 (q, 2H, J = 7.6 Hz), 1.44 (d,
3H, J = 6.9 Hz), 1.23 (t, 3H, J = 7.6 Hz); 13C NMR (100 MHz,
CDCl3): δ 170.5, 148.1, 143.2, 142.2, 138.3, 136.3, 134.5, 128.1,
127.9, 127.4, 126.8, 121.6, 121.4, 116.4, 47.0, 36.5, 28.4, 21.9, 15.6;
HRMS (ESI): MH+, found319.1794. C21H23N2O requires 319.1810.
20:80); FTIR (DCM): 3352, 2929, 1684, 1589 and 1527 cm-1; H
1
NMR (400 MHz, CDCl3): δ 9.71 (s, 1H), 8.79 (dd, 1H, J1 = 4.0 Hz,
J2 = 1.0 Hz), 8.74 (dd, 1H, J1 = 6.9 Hz, J2 = 1.7 Hz), 8.16 (dd, 1H, J1
= 8.2 Hz, J2 = 1.0 Hz), 7.55 – 7.44 (m, 3H), 7.28 – 7.23 (m, 1H),
7.09 (d, 1H, J = 7.7 Hz), 7.03 (d, 1H, J = 10.1 Hz), 6.88 (td, 1H, J1 =
8.5 Hz, J2 = 2.4 Hz), 3.27 – 3.24 (m, 1H), 2.92 – 2.81 (m, 2H), 1.91
– 1.85 (m, 1H), 1.75 – 1.69 (m, 1H), 0.87 (t, 3H, J = 7.3 Hz); 13C
NMR (100 MHz, CDCl3): δ 170.1, 163.1 (d, JC-F = 243 Hz), 148.1,
146.8 (d, JC-F = 6.8 Hz), 138.2, 136.3, 134.3, 129.9 (d, JC-F = 8.1 Hz),
127.9, 127.4, 123.5 (d, JC-F = 2.7 Hz), 121.6, 121.4, 116.4, 114.3 (d,
JC-F = 20.9 Hz), 113.3 (d, JC-F = 21 Hz), 45.3, 44.1 (d, JC-F = 1.3 Hz),
29.1, 12.0; HRMS (ESI): MH+, found 323.1576. C20H20FN2O
requires 323.1560.
3.2.3.
3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-N-(quinolin-8-
yl)butanamide (5j): Following the general procedure, 5j was
obtained after purification by column chromatography on silica gel
(EtOAc:Hexane = 20:80) as a brown colour solid (133 mg, 77%); Rf
= 0.4 (EtOAc:Hexane = 20:80); mp 96 – 98 oC; FTIR (DCM): 3352,
1
2965, 1682, 1589 and 1526 cm-1; H NMR (400 MHz, CDCl3): δ
9.74 (s, 1H), 8.79 – 8.76 (m, 2H), 8.13 – 8.08 (m, 1H), 7.51 – 7.4 (m,
3H), 6.87 – 6.82 (m, 3H), 4.20 – 4.19 (m, 4H), 3.45 – 3.40 (m, 1H),
2.86 (dd, 1H, J1 = 14.4 Hz, J2 = 6.8 Hz), 2.73 (dd, 1H, J1 = 14.8, J2 =
8.0 Hz), 1.39 (d, 3H, J = 6.9 Hz); 13C NMR (100 MHz, CDCl3): δ
170.4, 148.1, 143.5, 142.0, 139.4, 138.3, 136.3, 134.4, 127.9, 127.4,
121.6, 121.4, 119.8, 117.3, 116.4, 115.5, 64.4, 64.3, 47.0, 36.3, 22.0;
HRMS (ESI): MH+, found 349.1535. C21H21N2O3 requires 349.1552.
3.2.8. N-(Quinolin-8-yl)-3-(m-tolyl)pentanamide (7e): Following
the general procedure, 7e was obtained after purification by column
chromatography on silica gel (EtOAc:Hexane = 20:80) as a
colourless semi liquid (81 mg, 84%); Rf = 0.6 (EtOAc:Hexane =
1
20:80); FTIR (DCM): 3366, 2926, 1684, 1527 and 1484 cm-1; H
NMR (400 MHz, CDCl3): δ 9.73 (s, 1H), 8.78 – 8.77 (m, 2H), 8.14
(d, 1H, J = 8.2 Hz), 7.54 – 7.42 (m, 3H), 7.23 – 7.19 (m, 1H), 7.14 –
7.11 (m, 2H), 7.01 (d, 1H, J = 7.4 Hz), 3.23 – 3.17 (m, 1H), 2.88 (d,
2H, J = 7.4 Hz), 2.34 (s, 3H), 1.92 – 1.85 (m, 1H), 1.77 – 1.69 (m,
1H), 0.87 (t, 3H, J = 7.3 Hz); 13C NMR (100 MHz, CDCl3): δ 170.6,
148.0, 144.0, 138.3, 138.0, 136.3, 134.5, 128.4, 128.4, 127.9, 127.4,
127.2, 124.7, 121.5, 121.4, 116.4, 45.6, 44.3, 29.2, 21.5, 12.1;
HRMS (ESI): MH+, found 319.1823. C21H23N2O requires 319.1810.
3.2.4. 3-(3-Methoxyphenyl)-N-(quinolin-8-yl)hexanamide (6d):
Following the general procedure, 6d was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a colourless thick liquid (80 mg, 76%); Rf = 0.5 (EtOAc:Hexane =
1
20:80); FTIR (DCM): 3353, 2929, 1684, 1595 and 1528 cm-1; H
NMR (400 MHz, CDCl3): δ 9.71 (s, 1H), 8.78 – 8.76 (m, 2H), 8.13
(d, 1H, J = 8.2 Hz), 7.54 – 7.42 (m, 3H), 7.25 – 7.21 (m, 1H), 6.92 –
6.87 (m, 2H), 6.73 (dd, 1H, J1 = 8.2 Hz, J2 = 2.4 Hz), 3.79 (s, 3H),
3.34 – 3.30 (m, 1H), 2.86 (d, 2H, J = 7.4 Hz), 1.80 – 1.68 (m, 2H),
1.32 – 1.23 (m, 2H), 0.89 (t, 3H, J = 7.3 Hz); 13C NMR (100 MHz,
CDCl3): δ 170.4, 159.7, 148.0, 146.1, 138.3, 136.3, 134.4, 129.5,
127.9, 127.4, 121.5, 121.4, 120.0, 116.4, 113.4, 111.6, 55.1, 45.9,
42.5, 38.4, 20.6, 14.1; HRMS (ESI): MH+, found 349.1925
C22H25N2O2 requires 349.1916.
3.2.9. 3-(3,5-Dimethylphenyl)-N-(quinolin-8-yl)pentanamide (7f):
Following the general procedure, 7f was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a colourless solid (119 mg, 70%); Rf = 0.5 (EtOAc:Hexane = 20:80);
mp 74 – 75 oC; FTIR (DCM): 3355, 2924, 1689, 1602 and 1529 cm-
1; H NMR (400 MHz, CDCl3): δ 9.71 (s, 1H), 8.79 – 8.76 (m, 2H),
1
8.16 (dd, 1H, J1 = 8.3 Hz, J2 = 1.6 Hz), 7.55 – 7.44 (m, 3H), 6.92 (s,
2H), 6.82 (s, 1H), 3.17 – 3.12 (m, 1H), 2.86 (d, 2H, J = 7.4 Hz), 2.29
(s, 6H), 1.89 – 1.82 (m, 1H), 1.75 – 1.69 (m, 1H), 0.86 (t, 3H, J = 7.3
Hz); 13C NMR (100 MHz, CDCl3): δ 170.7, 148.0, 144.0, 138.3,
137.8, 136.3, 134.5, 128.1, 127.9, 127.4, 125.4, 121.5, 121.3, 116.4,
45.6, 44.2, 29.1, 21.4, 12.1; HRMS (ESI): MH+, found 333.1957
C22H25N2O requires 333.1967.
3.2.5. 3-(4-Acetylphenyl)-N-(quinolin-8-yl)pentanamide (7b):
Following the general procedure, 7b was obtained after purification
by column chromatography on silica gel (EtOAc:Hexane = 20:80) as
a brown colour semi solid (70 mg, 68%); Rf = 0.4 (EtOAc:Hexane =
1
20:80); FTIR (DCM): 3350, 2963, 1681, 1606 and 1575 cm-1; H
NMR (400 MHz, CDCl3): δ 9.69 (s, 1H), 8.74 (dd, 1H, J1 = 4.2 Hz,
J2 = 1.4 Hz), 8.70 (dd, 1H, J1 = 6.7 Hz, J2 = 2.0 Hz), 8.12 (dd, 1H, J1
= 8.2 Hz, J2 = 1.4 Hz), 7.89 (d, 1H, J = 8.2 Hz), 7.51 – 7.40 (m, 3H),
3.2.10.
3-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-N-(quinolin-8-
yl)pentanamide (7g): Following the general procedure, 7g was