PAPER
Peripheral Arylation of 5-Pyrazolones
1789
MS (CI+): m/z (%) = 456 (1) [M]+, 415 (3), 414 (11), 400 (13), 359
(23), 358 (100), 357 (35), 299 (6), 145 (2), 69 (2).
7.43 (m, 2 H), 7.38–7.33 (m, 1 H), 7.17–7.12 (m, 1 H), 2.63 (t,
J = 7.7 Hz, 2 H), 1.65–1.60 (m, 2 H), 1.57 (s, 9 H), 0.95 (t,
J = 7.4 Hz, 3 H).
tert-Butyl1-(2-Pyridinyl)-3-[3-(3¢-phenyl)biphenyl]-5-pyrazolyl
Carbonate (5k)
13C NMR (75 MHz, CDCl3): d = 152.4, 150.2, 150.0, 147.6, 146.8,
143.6, 140.9, 140.8, 138.4, 132.8, 131.7, 129.3, 128.9, 128.1, 127.4,
127.3, 127.1, 121.1, 114.5, 110.7, 85.2, 27.7.
MS (CI+): m/z (%) = 457 (10), 456 (33) [M]+, 412 (9), 398 (13), 396
(3), 357 (24), 356 (100), 355 (40), 326 (16).
1H NMR (300 MHz, CDCl3): d = 8.43–8.41 (m, 1 H), 8.15 (s, 1 H),
8.04 (d, J = 8.3 Hz, 1 H), 7.88–7.80 (m, 3 H), 7.69–7.45 (m, 9 H),
7.40–7.35 (m, 1 H), 7.22–7.17 (m, 1 H), 6.59 (s, 1 H), 1.58 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 152.3, 151.1, 149.7, 147.8, 146.5,
141.9, 141.8, 141.3, 138.5, 133.4, 129.3, 129.2, 128.9, 127.6, 127.5,
127.4, 126.4, 124.9, 124.7, 121.5, 115.2, 96.3, 84.9, 27.7.
MS (CI+): m/z (%) = 446 (5), 433 (4), 432 (12), 430 (4), 392 (4), 391
(28), 390 (100), 389 (33), 215 (7).
tert-Butyl 1-(2-Pyridinyl)-3-(4-biphenyl)-4-benzyl-5-pyrazolyl
Carbonate (5q)
1H NMR (300 MHz, CDCl3): d = 8.40–8.38 (m, 1 H), 8.05 (d,
J = 8.3 Hz, 1 H), 7.84–7.78 (m, 1 H), 7.71 (d, J = 8.3 Hz, 2 H),
7.62–7.58 (m, 4 H), 7.46–7.41 (m, 2 H), 7.36–7.31 (m, 1 H), 7.27–
7.25 (m, 4 H), 7.20–7.15 (m, 2 H), 4.01 (s, 2 H), 1.48 (s, 9 H).
tert-Butyl 1-(2-Pyridinyl)-3-[3-(1-naphthyl)phenyl]-5-pyra-
zolyl Carbonate (5l)
13C NMR (75 MHz, CDCl3): d = 152.3, 150.5, 149.5, 147.6, 146.6,
144.3, 141.0, 140.7, 139.5, 138.4, 132.1, 128.8, 128.5, 128.3, 128.1,
127.4, 127.2, 127.0, 126.2, 121.2, 114.5, 108.8, 85.2, 27.4.
MS (CI+): m/z (%) = 504 (5) [M]+, 447 (5), 446 (16), 405 (28), 404
(100), 403 (38), 356 (9), 326 (4).
1H NMR (300 MHz, CDCl3): d = 8.41–8.39 (m, 1 H), 8.01–7.87 (m,
6 H), 7.82–7.76 (m, 1 H), 7.57–7.41 (m, 6 H), 7.19–7.15 (m, 1 H),
6.55 (s, 1 H), 1.56 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 152.3, 151.0, 149.7, 147.7, 146.5,
141.3, 140.1, 138.5, 133.9, 132.9, 131.8, 130.3, 128.7, 128.3, 127.9,
127.5, 127.0, 126.2, 126.2, 125.9, 125.5, 124.7, 121.5, 115.1, 96.3,
84.9, 27.7.
MS (CI+): m/z (%) = 464 (2) [M]+, 420 (9), 406 (12), 390 (10), 364
(100), 363 (33), 272 (3), 144 (1), 69 (6).
tert-Butyl 1-[2-(3-Chloro)pyridinyl]-3-[3-(3¢,4¢-methylene-
dioxy)biphenyl]-5-pyrazolyl Carbonate (5r)
1H NMR (300 MHz, CDCl3): d = 8.55–8.53 (m, 1 H), 8.02 (s, 1 H),
7.94 (d, J = 8.0 Hz, 1 H), 7.82 (d, J = 7.2 Hz, 1 H), 7.48–7.37 (m,
3 H), 7.13–7.10 (m, 2 H), 6.88 (d, J = 7.8 Hz, 1 H), 6.70 (s, 1 H),
5.99 (s, 2 H), 1.52 (s, 9 H).
tert-Butyl 1-(2-Pyridinyl)-3-[3-(3¢-dimethylamino)biphenyl]-5-
pyrazolyl carbonate (5m)
13C NMR (75 MHz, CDCl3): d = 152.2, 148.4, 148.1, 147.3, 137.2,
146.8, 141.3, 139.8, 135.5, 133.4, 129.0, 128.9, 127.0, 125.3, 124.6,
124.5, 120.9, 108.6, 107.9, 101.2, 92.5, 85.5, 27.6.
MS (CI+): m/z (%) = 492 (1) [M]+, 463 (1), 447 (4), 419 (27), 392
(26), 391 (100), 279 (36), 205 (69), 111 (24), 69 (13).
1H NMR (300 MHz, CDCl3): d = 8.42–8.40 (m, 1 H), 8.07–8.01 (m,
2 H), 7.86–7.79 (m, 2 H), 7.59–7.56 (m, 1 H), 7.50–7.45 (m, 1 H),
7.36–7.30 (m, 1 H), 7.20–7.16 (m, 1 H), 7.01–6.97 (m, 2 H), 6.78–
6.75 (m, 1 H), 6.56 (s, 1 H), 3.02 (s, 6 H), 1.57 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 152.3, 151.2, 151.0, 149.7, 147.7,
146.5, 142.8, 142.3, 138.5, 133.1, 129.5, 129.5, 127.7, 124.9, 124.6,
121.5, 116.2, 115.1, 112.0, 111.9, 96.3, 84.9, 40.9, 27.7.
MS (CI+): m/z (%) = 457 (4) [M]+, 456 (2) [M]+, 413 (9), 399 (10),
397 (3), 364 (5), 358 (23), 357 (100), 356 (43), 138 (4), 69 (2).
tert-Butyl 1-(2-Pyrimidinyl)-3-[4-(3¢-phenyl)biphenyl]-5-pyra-
zolyl Carbonate (5s)
1H NMR (300 MHz, CDCl3): d = 8.80 (d, J = 4.8 Hz, 2 H), 8.03 (d,
J = 8.5 Hz, 2 H), 7.85–7.84 (m, 1 H), 7.73–7.44 (m, 9 H), 7.40–
7.35 (m, 1 H), 7.25–7.21 (m, 1 H), 6.62 (s, 1 H), 1.59 (s, 9 H).
tert-Butyl 1-(2-Pyridinyl)-3-[2-(3¢,4¢-methylenedioxy)biphenyl]-
5-pyrazolyl Carbonate (5n)
13C NMR (75 MHz, CDCl3): d = 158.7, 156.3, 152.5, 149.6, 147.5,
142.0, 141.8, 141.3, 131.4, 129.3, 128.9, 127.5, 127.4, 126.8, 126.5,
126.1, 118.8, 97.4, 85.2, 27.8.
MS (CI+): m/z (%) = 447 (1), 419 (2), 391 (6), 373 (20), 329 (4), 275
(32), 274 (19), 273 (100), 272 (13), 239 (16), 111 (2), 69 (7).
1H NMR (300 MHz, CDCl3): d = 8.38–8.36 (m, 1 H), 7.94–7.88 (m,
2 H), 7.82–7.76 (m, 1 H), 7.41–7.31 (m, 3 H), 7.17–7.13 (m, 1 H),
6.78 (m, 3 H), 5.96 (s, 2 H), 5.55 (s, 1 H), 1.51 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 152.3, 151.4, 149.5, 147.6, 147.4,
146.9, 145.1, 140.8, 138.5, 135.4, 131.8, 130.5, 129.2, 128.5, 127.5,
123.1, 121.3, 114.9, 110.3, 108.2, 101.1, 99.8, 84.7, 27.6.
MS (CI+): m/z (%) = 459 (18), 458 (62) [M]+, 457 (6), 419 (3), 415
(5), 414 (20), 400 (13), 359 (22), 358 (100), 357 (32), 183 (4), 138
(3), 123 (1).
Boc-Deprotection: 1-(2-Pyridinyl)-3-[4-(3¢,4¢-methylene-
dioxy)biphenyl]-5-hydroxypyrazole (6b); Typical Procedure
To a solution of 5b (286 mg, 0.62 mmol) in CH2Cl2 (10 mL), TFA
(707 mg, 6.2 mmol) was added. When the reaction was complete
(3 h as judged by TLC), the mixture was washed with H2O (3 × 5
mL), dried over anhydrous MgSO4, and concentrated to dryness.
The crude material was purified by column chromatography on sil-
ica gel (hexane–EtOAc, 10:1) to afford 6b.
1-(2-Pyridinyl)-3-[2-(3¢-phenyl)biphenyl]-5-hydroxypyrazole
(6o)
1H NMR (300 MHz, CDCl3): d = 8.10–8.06 (m, 2 H), 7.67 (s, 1 H),
7.56–7.47 (m, 5 H), 7.40–7.26 (m, 9 H), 6.04 (s, 1 H).
Yield: 155 mg (70%).
1H NMR (300 MHz, CDCl3): d = 8.29–8.27 (m, 1 H), 8.08–8.05 (m,
1 H), 7.93–7.87 (m, 3 H), 7.59–7.55 (m, 2 H), 7.19–7.14 (m, 1 H),
7.12–7.09 (m, 2 H), 6.90–6.88 (m, 1 H), 6.00 (s, 2 H), 5.96 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 157.5, 152.4, 148.3, 147.3, 145.2,
141.1, 140.0, 135.2, 131.7, 127.1, 126.3, 120.7, 120.0, 112.4, 108.7,
108.2, 107.6, 106.7, 101.3, 101.2, 85.9.
13C NMR (75 MHz, CDCl3): d = 159.4, 155.7, 147.1, 143.3, 142.3,
142.2, 140.4, 140.4, 138.0, 132.4, 131.9, 130.6, 128.8, 128.1, 127.4,
126.9, 126.3, 119.8, 113.7, 96.6, 90.5.
HRMS (EI): m/z calcd for C26H19N3O: 389.1528; found: 389.1523.
tert-Butyl 1-(2-Pyridinyl)-3-(4-biphenyl)-4-propyl-5-pyrazolyl
Carbonate (5p)
HRMS (EI): m/z calcd for C21H15N3O3: 357.1113; found: 357.1121.
1H NMR (300 MHz, CDCl3): d = 8.40–8.37 (m, 1 H), 8.00 (d,
J = 8.3 Hz, 1 H), 7.84–7.75 (m, 3 H), 7.70–7.63 (m, 4 H), 7.48–
Synthesis 2011, No. 11, 1783–1791 © Thieme Stuttgart · New York