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Org aP nl ei ca s &e dB oi o nmo to al ed cj uu sl at rm Ca hr ge imn si stry
Journal Name
28.3 (q, J = 6.0 Hz), 129.3, 136.4, 145.2, 151.0, 177.1; F NMR (100 MHz, CDCl3)
ARTICLE
1
9
1
-1
DOI: 10.1039/C6OB01325B
(368 MHz, CDCl3) -60.7; IR (KBr, / cm ) 3442, 2972, 1690, 124.0 (q, J = 273 Hz), 124.5, 125.9 (q, J = 5.6 Hz), 127.2, 129.8,
1
9
1
1
598, 1520, 1497, 1400, 1362, 1331, 1308, 1238, 1153, 1122, 133.1 (q, J = 1.9 Hz), 136.0, 137.5, 138.0, 144.3, 149.0; F NMR
+
-1
113, 964, 828, 788; HRMS (ESI ) Calcd for C H F N NaO (368 MHz, CDCl3)
-59.5; IR (KBr,
/ cm ) 3435, 3270, 2923,
15 15 3 2
+
([M+Na] ) 319.1034, Found 319.1047.
1580, 1509, 1478, 1378, 1317, 1167, 1113, 876, 734, 662;
+
+
tert-Butyl(5-(trifluoromethyl)quinolin-8-yl)carbamate (3s). HRMS (ESI ) Calcd for C H F N NaO S ([M+Na] ) 389.0547,
17
13
3
2
2
4
9% yield; white solid; R = 0.53 (hexane/ethyl acetate = 5/1); Found 389.0559.
f
1
H NMR (400 MHz, CDCl3)
1.59 (s, 9H), 7.57 (dd, J = 8.5, 4.0
Typical procedure for copper-catalyzed trifluoromethylation of 8-
aminoquinoline derivatives 4.
Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 8.43 (d, J = 8.5 Hz, 1H), 7.81 (dt,
J = 8.5, 1.8 Hz, 1H), 7.81 (dd, J = 4.0, 1.8 Hz, 1H), 9.24 (brs, 1H);
13
A mixture of A mixture CuCl (0.6 mg, 6.25
mol, 5.0 mol%) and
99.8 mg,
C NMR (100 MHz, CDCl3)
1.0 Hz), 122.7, 124.3, 124.4 (q, J = 273 Hz), 126.5 (q, J = 5.6
28.3, 81.1, 112.0, 118.2 (q, J =
1
-trifluoromethyl-1,2-benziodoxol-3(1H) one
-
(2,
3
19
0.125 mmol, 1.0 equiv) was added to a solution of 8-
quinolinylamine (4a, 28.6 mg, 0.125 mmol, 1.0 equiv) in 1,2-
dichloroethane (1.25 mL) in a sealed tube. The mixture was
then stirred at 25 ºC for 18 h. The product was isolated from
starting material and other byproducts by column
chromatography on silica gel or recycling preparative HPLC to
give regioisomers (12.7 mg, 48% yield).
Hz), 133.0 (q, J = 1.9 Hz), 138.0, 138.9, 148.4, 152.5; F NMR
-1
(368 MHz, CDCl3)
-59.2; IR (KBr,
/ cm ) 3351, 2990, 2925,
1
1
722, 1581, 1533, 1499, 1456, 1394, 1373, 1335, 1318, 1254,
213, 1165, 1140, 1125, 1113, 1009, 842, 684; HRMS (ESI )
+
+
Calcd for C H F N NaO ([M+Na] ) 335.0983, Found 335.0974.
15
15
3
2
2
tert-Butyl(6-methoxy-5-(trifluoromethyl)quinolin-8-
yl)carbamate (3t). 49% yield; pale yellow solid; R = 0.48
f
1
N-(Trifluoromethylquinolin-8-yl)benzylamine (5b). 49%
yield (5- and 7-position isomers); brown oil; H NMR (400 MHz,
(hexane/ethyl acetate = 5/1); H NMR (400 MHz, CDCl )
1.59
3
1
(
8
s, 9H), 4.06 (s, 3H), 7.50 (dd, J = 9.0, 4.0 Hz, 1H), 8.38 (s, 1H),
.52 (dt, J = 9.0, 1.4 Hz, 1H), 8.69 (dd, J = 4.0, 1.4 Hz, 1H), 9.30
CDCl3)
8.5 Hz, 1H), 7.09 (brs, 1H), 7.30-7.48 (m, 5H), 7.51 (dd, J = 8.5,
.0 Hz, 1H), 7.69 (d, J = 8.1 Hz, 1H), 8.56 (dt, J = 8.5,1.8 Hz, 1H),
8.77 (dd, J = 4.0, 1.8 Hz, 1H); (7-position isomer) 4.72 (s, 2H),
7.14 (d, J = 9.0 Hz, 1H), 7.30-7.48 (m, 7H), 7.60 (d, J = 9.0 Hz,
(5-position isomer) 4.60 (d, J = 5.4 Hz, 2H), 6.55 (d, J =
1
3
(brs, 1H); C NMR (100 MHz, CDCl3)
28.3, 56.9, 81.2, 101.7,
4
1
02.6 (q, J = 30.0 Hz), 123.2, 125.2 (q, J = 274 Hz), 126.3, 132.5
1
9
(q, J = 5..6 Hz), 133.4, 140.1, 145.6, 152.5, 158.3; F NMR (368
-
1
MHz, CDCl3)
1
1
-52.5; IR (KBr, / cm ) 3350, 2979, 2937, 1727,
1
H) , 8.07 (dd, J = 8.1, 1.8 Hz, 1H), 8.74 (dd, J = 4.5, 1.8 Hz, 1H);
624, 1581, 1534, 1494, 1466, 1413, 1392, 1367, 1291, 1250,
222, 1168, 1097, 1082, 1011, 780, 691; HRMS (ESI ) Calcd for
1
3
+
C NMR (100 MHz, CDCl3)
111.6 (q, J = 31.0 Hz), 122.6, 125.2 (q, J = 272 Hz), 124.9, 127.2
q, J = 5.6 Hz), 127.3, 127.4, 128.7, 132.8 (q, J = 1.9 Hz), 137.7,
38.2, 147.2, 147.4; (7-position isomer) 51.5, 109.1 (q, J = 31.0
Hz), 115.0, 123.0, 125.3 (q, J = 272 Hz), 124.8 (q, J = 5.6 Hz),
(5-position isomer) 47.2, 102.1,
+
C H F N NaO ([M+Na] ) 365.1089, Found 365.1079.
1
6
17
3
2
3
(
1
1
,1-Dimethyl-3-(5-(trifluoromethyl)quinolin-8-yl)urea (3u).
8% yield; pale yellow solid; R = 0.35 (hexane/ethyl acetate =
f
/1); H NMR (400 MHz, CDCl )
.5 Hz, 1H), 7.88 (d, J = 8.9 Hz, 1H), 8.59 (d, J = 8.5 Hz, 1H), 8.48
4
1
4
1
3.18 (s, 6H), 7.56 (dd, J = 8.9,
3
1
1
28.1, 128.6, 129.6, 136.0, 139.6, 140.2, 144.8 (q, J = 1.9 Hz),
47.4, 147.7; F NMR (368 MHz, CDCl3)
19
(5-position isomer) -
/ cm ) 3394, 3065,
(dd, J = 8.5, 1.8 Hz, 1H), 8.83 (dd, J = 4.5, 1.8 Hz, 1H), 9.60 (brs,
-1
1
3
58.6; (7-position isomer) -55.2; IR (neat,
1
H); C NMR (100 MHz, CDCl3) 36.4, 112.1, 117.4 (q, J = 31.0
3
032, 2926, 2856, 1613, 1577, 1525, 1503, 1454, 1388, 1359,
Hz), 122.6, 124.3, 124.5 (q, J = 272 Hz), 126.8 (q, J = 5.6 Hz),
1
MHz, CDCl3)
1
1
1
9
1318, 1263, 1223, 1178, 1143, 1103, 1263, 1223, 1178, 1143,
1103, 1031, 948, 816, 792, 735, 697; HRMS (ESI ) Calcd for
33.2 (q, J = 1.9 Hz), 138.2, 139.6, 148.1, 155.0; F NMR (368
+
-
1
-59.1; IR (KBr, / cm ) 3364, 2921, 1669, 1581,
548, 1504, 1394, 1335, 1316, 1223, 1173, 1140, 1106, 1086,
+
C H F N Na ([M+Na] ) 325.0928, Found 325.0924.
17 13 3 2
+
N-(5-Trifluoromethylquinolin-8-yl)dibenzylamine (5c). 47%
yield; yellow oil; R = 0.50 (hexane/ethyl acetate = 5/1); H
f
007, 951, 866, 791; HRMS (ESI ) Calcd for C H F N NaO
1
3 12 3 3
1
+
([M+Na] ) 306.0830, Found 306.0826.
NMR (400 MHz, CDCl3)
4.82 (s, 4H), 7.18-7.36 (m, 10H), 6.84
N-(5-(Trifluoromethyl)quinolin-8-yl)-methanesulfonamide
1
(d, J = 8.1 Hz, 1H), 7.48 (dd, J = 9.0, 4.0 Hz, 1H), 7.61 (d, J = 8.1
Hz, 1H), 8.43 (d, J = 9.0, 1.8 Hz, 1H), 8.90 (dd, J = 4.0, 1.8 Hz,
(
3
(
3v). 27% yield; white solid; H NMR (400 MHz, CDCl )
3.12 (s,
H), 7.65 (dd, J = 9.0, 4.5 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.92
d, J = 8.1 Hz, 1H), 8.53 (dt, J = 9.0, 1.4 Hz, 1H), 8.91 (dd, J = 4.5,
3
1
3
1
H); C NMR (125 MHz, CDCl3)
56.6, 114.5, 116.7 (q, J = 31.0
1
3
Hz), 121.8, 124.8 (q, J = 272 Hz), 125.7 (q, J = 5.6 Hz), 126.1,
1
1
1
.4 Hz, 1H), 9.24 (brs, 1H); C NMR (100 MHz, CDCl3) 39.8,
1
1
27.0, 128.0, 128.3, 132.7 (q, J = 1.9 Hz), 138.3, 142.2, 147.3,
50.6; F NMR (368 MHz, CDCl3)
11.5, 120.3 (q, J = 31.0 Hz), 123.4, 124.0 (q, J = 273 Hz), 124.7,
26.1 (q, J = 5.6 Hz), 133.3 (q, J = 1.9 Hz), 137.9, 138.1, 149.3;
19
-1
-59.0; IR (neat, / cm )
19
-1
3086, 3063, 3029, 2929, 2852, 1726, 1605, 1567, 1508, 1495,
F NMR (368 MHz, CDCl3)
-59.5; IR (KBr,
/ cm ) 3434, 3303,
1
453, 1365, 1324, 1219, 1180, 1096, 1074, 1044, 1029, 1008,
1
9
579, 1510, 1482, 1368, 1323, 1149, 1121, 1105, 1073, 1038,
76, 880, 822, 799, 733; HRMS (ESI ) Calcd for C H F N NaO S
+
+
956, 918, 821, 791, 735, 699; HRMS (ESI ) Calcd for
11
9
3
2
2
+
+
C H F N Na ([M+Na] ) 415.1398, Found 415.1392.
24 19 3 2
([M+Na] ) 313.0234, Found 313.0233.
N-(5-(Trifluoromethyl)quinolin-8-yl)-p-toluenesulfonamide
3w). 34% yield; colorless solid; H NMR (500 MHz, CDCl )
3
Trifluoromethylation of lamidoquinoline 1a in the presence of a
radical scavenger.
1
(
2
1
.33 (s, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.57 (dd, J = 8.6, 4.0 Hz,
H), 7.75-7.82 (m, 2H), 7.85 (d, J = 8.0 Hz, 2H), 8.43 (d, J = 8.6
A mixture of CuCl2 (0.60 mg, 6.25 mol, 5.0 mol%), 1-
trifluoromethyl-1,2-benziodoxol-3(1H)-one (2, 99.8 mg, 0.125 mmol,
13
Hz, 1H), 8.85 (dd, J = 4.0, 1.2 Hz, 1H), 9.25 (brs, 1H); C NMR
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