9276
C.B. Baltus et al. / Tetrahedron 68 (2012) 9272e9277
[C13H13NþH]þ 184.1121. Elemental analysis found: C, 85.4; H, 7.2; N,
J¼8.2 Hz), 2.34 (s, 3H). 13C NMR (DMSO-d6)
d (ppm): 165.5, 138.4,
7.6. C13H13N requires C, 85.2; H, 7.2; N, 7.6.
136.8, 136.3, 135.2, 134.9, 131.6, 129.5 (2C), 128.4 (2C), 127.7 (2C),
126.5 (2C), 126.1 (2C), 120.6 (2C), 20.7. HRMS-ES (m/z) found
288.1384, calcd for [C20H17NOþH]þ 288.1383. Elemental analysis
found C, 83.2; H, 6.0; N, 4.7. C20H17NO requires C, 83.6, H, 6.0, N,
4.9.
4.3.2. 6-p-Tolylpyridin-3-amine 4b. Off-white solid, 80 mg (99%
yield, 0.44 mmol scale). Mp: 96e98 ꢀC. IR (cmꢁ1): 3461, 3308, 3193,
3035, 2917, 1629, 1595, 1562, 1481, 1629, 1562, 1421, 1321, 1299,
1244, 1146, 1038, 1018, 816, 749, 646. 1H NMR (CDCl3)
d (ppm): 8.16
(d, 1H, J¼2.7 Hz), 7.78 (d, 2H, J¼8.2 Hz), 7.51 (d, 1H, J¼8.7 Hz), 7.22
4.4.5. N-(40-Methylbiphenyl-4-yl)methanesulfonamide
6f. White
(d, 2H, J¼8.2 Hz), 7.03 (dd, 1H, J1¼2.7 Hz, J2¼8.7 Hz), 3.74e3.65 (brs,
solid, 94 mg (82% yield, 0.44 mmol scale). Crystallisation from
CH2Cl2/MeOH. Mp: 175e180 ꢀC. IR (cmꢁ1): 3273, 3027, 2938, 2864,
1610, 1500, 1465, 1450, 1407, 1394, 1332, 1300, 1149, 969, 924, 838,
2H, NH2), 2.38 (s, 3H). 13C NMR (CDCl3)
d (ppm): 148.1, 141.1,
137.6, 136.9, 136.6, 129.4 (2C), 125.9 (2C), 122.5, 120.5, 21.2.
HRMS-ES (m/z) found 185.1071, calcd for [C12H12N2þH]þ 185.1073.
Elemental analysis found C, 78.0; H, 6.6; N, 15.0. C12H12N2 requires
C, 78.2; H, 6.6; N, 15.2.
805, 752. 1H NMR (CDCl3)
d
(ppm): 7.55 (d, 2H, J¼8.4 Hz), 7.44 (d,
2H, J¼8.4 Hz), 7.28e7.21 (m, 4H), 6.37e6.29 (brs, 1H), 3.03 (s, 3H),
2.38 (s, 3H). 13C NMR (CDCl3)
(ppm): 138.6, 137.3, 137.1, 135.5,
d
129.6 (2C), 128.2 (2C), 126.7 (2C), 121.3 (2C), 39.5, 21.1. Elemental
analysis found C, 63.7; H, 5.9; N, 5.3. C14H15NO2S requires C, 64.3; H,
5.8; N, 5.4.
4.4. General amide coupling procedure
4.4.1. N-(40-Methylbiphenyl-4-yl)acetamide
(0.33 mmol, 60 mg), 5b (0.70 mmol, 1.104 g mLꢁ1, 50
6b. Compound
4a
mL), PS-NMM
4.4.6. N-(6-p-Tolylpyridin-3-yl)cyclopropanecarboxamide 6g. White
solid, 26 mg (34% yield, 0.30 mmol scale). Crystallisation from
CH2Cl2/MeOH. Mp: 213e215 ꢀC. IR (cmꢁ1): 3288, 3013, 2918,
2966, 1659, 1601, 1538, 1509, 1478, 1397, 1368, 1286, 1198, 1183,
(0.70 mmol, 175 mg) and CH2Cl2 (10 mL) were stirred at rt for 48 h.
The mixture was filtered and the filtrate was concentrated under
reduced pressure. The crude product was purified by chromatog-
raphy on silica gel, CH2Cl2/EtOAc 9:1, to give 77 mg of the pure
expected product as an off-white solid (99% yield). Crystallisation
from CH2Cl2/MeOH. Mp: 208e210 ꢀC. IR (cmꢁ1): 3130, 3109, 3030,
2915, 2855, 1605, 1530, 1498, 1324, 1119, 1066, 920, 844, 811, 719.
1033, 953, 811. 1H NMR (CDCl3)
d (ppm): 8.62e8.52 (brs, 1H),
8.25 (d, 1H, J¼8.7 Hz), 7.85 (d, 2H, J¼7.9 Hz), 7.68 (d, 1H,
J¼8.7 Hz), 7.50e7.44 (m, 1H), 7.26 (d, 2H, J¼7.9 Hz), 2.40 (s, 3H),
1.59e1.52 (m, 1H), 1.16e1.11 (m, 2H), 0.93e0.88 (m, 2H). 13C NMR
1H NMR (CDCl3)
7.23 (d, 2H, J¼8.4 Hz), 7.21e7.17 (m, 1H), 2.39 (s, 3H), 2.20 (s, 3H).
13C NMR (CDCl3)
(ppm): 168.2, 137.6, 137.2, 136.9 (2C), 129.5 (2C),
d
(ppm): 7.57e7.51 (m, 4H), 7.46 (d, 2H, J¼8.4 Hz),
(CDCl3) d (ppm): 172.3, 140.4, 138.6, 136.1, 133.4, 129.5 (3C),
127.8, 126.4 (2C), 120.2, 21.4, 15.8, 8.3 (2C). HRMS-ES (m/z) found
253.1332, calcd for [C16H16N2OþH]þ 253.1335. Elemental analy-
sis found C, 75.8; H, 6.4; N, 11.0. C16H16N2O requires C, 76.2; H,
6.4; N, 11.1.
d
127.4 (2C), 126.7 (2C), 120.1 (2C), 24.6, 21.1. HRMS-ES (m/z) found
226.1220, calcd for [C15H15NOþH]þ 226.1226. Elemental analysis
found C, 80.0; H, 6.8; N, 6.6. C15H15NO requires C, 80.0; H, 6.7; N,
6.2.
4.4.7. N-(40-Methylbiphenyl-3-yl)cyclopropanecarboxamide
6h. White solid, 186 mg (74% yield, 1.00 mmol scale). Crystal-
lisation from CH2Cl2/MeOH. Mp: 183e185 ꢀC. IR (cmꢁ1): 3279,
3244, 3019, 2919, 1655, 1610, 1556, 1480, 1418, 1384, 1310, 1232,
4.4.2. Methyl 3-(40-methylbiphenyl-4-ylamino)-3-oxopropanoate
6c. White solid, 123 mg, (97% yield, 0.45 mmol scale). Crystal-
lisation from CH2Cl2/MeOH. Mp: 158e160 ꢀC. IR (cmꢁ1): 3280,
3029, 2954, 2919, 1741, 1654, 1602, 1536, 1500, 1434, 1417, 1346,
962, 865, 816, 735, 692. 1H NMR (CDCl3)
d
(ppm): 7.83e7.70 (brs,
1H), 7.50e7.42 (m, 3H), 7.41e7.36 (m, 1H), 7.36 (dd, 1H, J1
and
1277, 1249, 1150, 1018, 806. 1H NMR (CDCl3)
d
(ppm): 9.21e9.07
¼7.8 Hz), 7.31 (d, 1H, J¼7.8 Hz), 7.22 (d, 2H, J¼8.2 Hz), 2.38 (s, 3H),
2
(brs, 1H), 7.55 (d, 2H, J¼9.0 Hz), 7.48 (d, 2H, J¼9.0 Hz), 7.40 (d, 2H,
1.56e1.45 (m, 1H), 1.14e1.07 (m, 2H), 0.89e0.80 (m, 2H). 13C NMR
(CDCl3) (ppm): 171.9, 142.1, 138.6, 137.9, 137.4, 129.5 (2C), 129.4,
J¼8.0 Hz), 7.17 (d, 2H, J¼8.0 Hz), 3.75 (s, 3H), 3.44 (s, 2H), 2.32 (s,
d
3H). 13C NMR (CDCl3)
d
(ppm): 170.5,162.6, 137.6, 137.4,136.9, 136.4,
127.1 (2C), 122.7, 118.3 (2C), 21.2, 15.9, 8.1 (2C). HRMS (m/z) found
252.1386, calcd for [C17H17NOþH]þ 252.1383. Elemental analysis
(%) found C, 81.1; H, 6.6; N, 5.3, C17H17NO requires C, 81.2; H, 6.8; N,
5.6.
129.5 (2C), 127.4 (2C), 126.7 (2C), 120.4 (2C), 52.7, 41.2, 21.1. HRMS-
ES (m/z) found 284.1280, calcd for [C17H17NO3þH]þ 284.1281. Ele-
mental analysis found C, 71.9; H, 6.2; N, 4.7. C17H17NO3 requires C,
72.1; H, 6.1; N, 4.9.
4.4.8. N-(40-Methylbiphenyl-3-yl)acetamide 6i. White solid, 164 mg
(89% yield, 0.82 mmol scale). Crystallisation from CH2Cl2/MeOH.
Mp: 138e141 ꢀC. IR (cmꢁ1): 3260, 3063, 2919, 1666, 1609, 1555,
4.4.3. 2-(Dimethylamino)-N-(40-methylbiphenyl-4-yl)acetamide
6d. White solid, 95 mg, (81% yield, 0.44 mmol scale). Crystallisation
from CH2Cl2/MeOH. Mp: 99e100 ꢀC. IR (cmꢁ1): 3283, 3027, 2977,
2947, 2817, 2763,1669,1588,1502,1471,1417,1397,1323,1269,1143,
1485, 1417, 1364, 1316,1260, 782, 692, 817. 1H NMR (CDCl3)
d (ppm):
7.72e7.66 (brs, 1H), 7.52e7.45 (m, 3H), 7.37 (dd, 1H, J1 and 2¼7.6 Hz),
1049, 986, 804, 732. 1H NMR (CDCl3)
d (ppm): 9.24e9.08 (brs, 1H),
7.32 (d, 1H, J¼7.6 Hz), 7.24 (d, 2H, J¼8.0 Hz), 7.25e7.17 (brs, 1H), 2.39
7.65 (d, 2H, J¼8.6 Hz), 7.55 (d, 2H, J¼8.6 Hz), 7.47 (d, 2H, J¼8.0 Hz),
(s, 3H), 2.20 (s, 3H). 13C NMR (CDCl3)
d (ppm): 168.3, 142.2, 138.3,
7.23 (d, 2H, J¼8.0 Hz), 3.09 (s, 2H), 2.42e2.36 (m, 9H). 13C NMR
137.9, 137.4, 129.6 (2C), 129.4, 127.1 (2C), 123.1, 118.6, 118.5, 24.8,
21.2. HRMS-ES (m/z) found 226.1227, calcd for [C15H15NOþH]þ,
226.1226. Elemental analysis (%) found C, 79.8; H, 6.6; N, 6.1.
C15H15NO requires C, 80.0; H, 6.7; N, 6.2.
(CDCl3)
d (ppm): 168.7, 137.7, 136.9, 136.8, 136.7, 129.5 (2C), 127.4
(2C), 126.7 (2C), 119.7 (2C), 63.7, 46.0 (2C), 21.1. HRMS-ES (m/z)
found 269.1651, calcd for [C17H20N2OþH]þ 269.1648. Elemental
analysis found C, 76.0; H, 7.5; N, 10.2. C17H20N2O requires C, 76.1; H,
7.5; N, 10.4.
4.4.9. N-(40-Methylbiphenyl-3-yl)methanesulfonamide
6j. White
solid, 103 mg (40% yield, 1.00 mmol scale). Crystallisation from
CH2Cl2/MeOH. Mp: 83e84 ꢀC. IR (cmꢁ1): 3252, 3033, 2925, 1606,
1469, 1408, 1386, 1318, 1302, 1144, 967, 839, 881, 815, 783, 742, 964.
4.4.4. N-(40-Methylbiphenyl-4-yl)benzamide
6e. White
solid,
115 mg (91% yield, 0.44 mmol scale). Mp: 214e215 ꢀC. IR (cmꢁ1):
3346, 3050, 3032, 2912, 2855, 1652, 1595, 1514, 1397, 1252, 1139,
1H NMR (CDCl3)
d
(ppm): 7.47 (d, 2H, J¼8.0 Hz), 7.43e7.39 (m, 3H),
7.26 (d, 2H, J¼8.0 Hz), 7.20e7.16 (m, 1H), 6.40e6.30 (brs, 1H), 3.04
(s, 3H), 2.40 (s, 3H). 13C NMR (CDCl3)
(ppm): 143.0, 137.8, 137.1,
137.0, 130.1, 129.6 (2C), 127.0 (2C), 124.1, 119.2, 119.1, 39.5, 21.1.
1026, 1003, 840, 805, 711, 691. 1H NMR (DMSO-d6)
d (ppm):
10.39e10.26 (brs, 1H), 7.97 (d, 2H, J¼8.6 Hz), 7.87 (d, 2H,
d
J¼8.6 Hz), 7.65 (d, 2H, J¼9.0 Hz), 7.61e7.51 (m, 5H), 7.26 (d, 2H,