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tle product. 1H NMR (400 MHz, CDCl3) d 9.35 (br s, 1H, –NH–), 7.44
(d, J = 1.8 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d, J = 8.7 Hz, 2H), 2.96 (t,
J = 7.3 Hz, 2H), 2.37 (s, 3H), 1.77–1.69 (m, 2H), 1.42–1.33 (m, 4H),
0.91 (t, J = 6.9 Hz, 3H). MS, m/z = 478 ([M+H]+).
dropwise thereto, and the mixture was reacted for 30 min. Then,
the mixture was returned to room temperature and further reacted
for 16 h. After completion of the reaction, the reaction mixture was
pour into saturated NaHCO3 solution (30 mL) and extracted with
EtOAc (50 mL). The organic layer was washed successively with
water, dried over MgSO4 and evaporated under vacuum. The resi-
due was further purified by prep HPLC to provide the title com-
pound (90.0 mg, 0.18 mmol, 30%) as a pale yellow solid. 1H NMR
4.2.23. N-Butyryl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazole-3-carboxamide (16i)
The procedure described for the synthesis of 16a was applied to
the amide intermediate (7) and butanoyl chloride providing the ti-
tle product. 1H NMR (400 MHz, CDCl3) d 9.36 (br s, 1H, –NH–), 7.45
(d, J = 2.3 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d, J = 8.3 Hz, 2H), 2.94 (t,
J = 7.3 Hz, 2H), 2.37 (s, 3H), 1.81–1.71 (m, 2H), 1.03 (t, J = 7.3 Hz,
3H). MS, m/z = 450 ([M+H]+).
(400 MHz, CDCl3)
d 8.85 (br s, 1H, –NH–, imide), 8.36 (t,
J = 5.5 Hz, 1H, –NH–, amide), 7.44 (d, J = 2.3 Hz, 1H), 7.34–7.23
(m, 4H), 7.06 (d, J = 8.2 Hz, 2H), 3.35 (q, J = 6.0 Hz, 2H), 2.36 (s,
3H), 1.64–1.56 (m, 2H), 1.42–1.29 (m, 6H), 0.90 (t, J = 6.44 Hz,
3H). MS, m/z = 507 ([M+H]+).
4.2.24. N-Acetyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazole-3-carboxamide (16j)
4.2.30. 5-(4-Chlorophenyl)-N-(cyclohexylcarbamoyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (17b)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and cyclohexyl isocyanate providing
the title product. 1H NMR (400 MHz, CDCl3) d 8.83 (br s, 1H, –
NH–, imide), 8.32 (d, J = 8.2 Hz, 1H, –NH–, amide), 7.44 (d,
J = 2.3 Hz, 1H), 7.33–7.23 (m, 4H), 7.06 (d, J = 8.2 Hz, 2H), 3.84–
3.74 (m, 1H), 2.36 (s, 3H), 2.03–1.96 (m, 2H), 1.78–1.71 (m, 2H),
1.65–1.57 (m, 1H), 1.46–1.21 (m, 5H). MS, m/z = 505 ([M+H]+).
The procedure described for the synthesis of 16a was applied to
the amide intermediate (7) and acetyl chloride providing the title
product. 1H NMR (400 MHz, CDCl3) d 9.39 (br s, 1H, –NH–), 7.45
(d, J = 2.2 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d, J = 8.6 Hz, 2H), 2.60
(s, 3H), 2.38 (s, 3H). MS, m/z = 422 ([M+H]+).
4.2.25. 5-(4-Chlorophenyl)-N-(cyclohexanecarbonyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (16k)
The procedure described for the synthesis of 16a was applied to
the amide intermediate (7) and cyclohexanecarbonyl chloride pro-
viding the title product. 1H NMR (400 MHz, CDCl3) d 9.31 (br s, 1H,
–NH–), 7.44 (d, J = 1.8 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d,
J = 8.2 Hz, 2H), 3.29–3.21 (m, 1H), 2.38 (s, 3H), 2.03–1.96 (m, 2H),
1.86–1.78 (m, 2H), 1.75–1.68 (m, 1H), 1.56–1.33 (m, 4H), 1.31–
1.20 (m, 1H). MS, m/z = 490 ([M+H]+).
4.2.31. 5-(4-Chlorophenyl)-N-(cycloheptylcarbamoyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (17c)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and cycloheptyl isocyanate providing
the title product. 1H NMR (400 MHz, CDCl3) d 8.81 (br s, 1H, –
NH–, imide), 8.38 (d, J = 7.8 Hz, 1H, –NH–, amide), 7.44 (d,
J = 2.3 Hz, 1H), 7.33–7.23 (m, 4H), 7.06 (d, J = 8.7 Hz, 2H), 4.03–
3.94 (m, 1H), 2.36 (s, 3H), 2.04–1.96 (m, 2H), 1.71–1.49 (m, 10H).
MS, m/z = 519 ([M+H]+).
4.2.26. 5-(4-Chlorophenyl)-N-(cyclopentanecarbonyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (16l)
Theproceduredescribedforthesynthesisof16awasappliedtothe
amide intermediate (7) and cyclopentanecarbonyl chloride providing
the title product. 1H NMR (400 MHz, CDCl3) d 9.33 (br s, 1H, –NH–),
7.44 (d, J = 1.8 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d, J = 8.7 Hz, 2H),
3.74–3.66 (m, 1H), 2.38 (s, 3H), 2.06–1.97 (m, 2H), 1.95–1.86 (m,
2H), 1.80–1.71 (m, 2H), 1.69–1.60 (m, 2H). MS, m/z = 476 ([M+H]+).
4.2.32. 5-(4-Chlorophenyl)-N-(cyclohexylmethylcarbamoyl)-1-
(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (17d)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and cyclohexanemethyl isocyanate
providing the title product. 1H NMR (400 MHz, CDCl3) d 8.86 (br
s, 1H, –NH–, imide), 8.42 (t, J = 5.9 Hz, 1H, –NH–, amide), 7.44 (d,
J = 1.8 Hz, 1H), 7.33–7.23 (m, 4H), 7.06 (d, J = 8.2 Hz, 2H), 3.21 (t,
J = 6.4 Hz, 2H), 2.36 (s, 3H), 1.84–1.64 (m, 5H), 1.62–1.52 (m, 1H),
1.32–1.12 (m, 3H), 1.04–0.94 (m, 2H). MS, m/z = 519 ([M+H]+).
4.2.27. 5-(4-Chlorophenyl)-N-(cyclobutanecarbonyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (16m)
The procedure described for the synthesis of 16a was applied to
the amide intermediate (7) and cyclobutanecarbonyl chloride pro-
viding the title product. 1H NMR (400 MHz, CDCl3) d 9.28 (br s, 1H,
–NH–), 7.44 (d, J = 1.8 Hz, 1H), 7.34–7.24 (m, 4H), 7.06 (d,
J = 8.2 Hz, 2H), 4.06–3.97 (m, 1H), 2.44–2.28 (m, 7H), 2.09–1.99
(m, 1H), 1.97–1.86 (m, 1H). MS, m/z = 462 ([M+H]+).
4.2.33. 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(isopropylc-
arbamoyl)-4-methyl-1H-pyrazole-3-carboxamide (17e)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and isopropyl isocyanate providing the
title product. 1H NMR (400 MHz, CDCl3) d 8.82 (br s, 1H, –NH–,
imide), 8.24 (d, J = 7.8 Hz, 1H, –NH–, amide), 7.44 (d, J = 2.3 Hz,
1H), 7.33–7.23 (m, 4H), 7.06 (d, J = 8.7 Hz, 2H), 4.14–4.04 (m,
1H), 2.36 (s, 3H), 1.26 (d, J = 6.4 Hz, 6H). MS, m/z = 465 ([M+H]+).
4.2.28. 5-(4-Chlorophenyl)-N-(cyclopropanecarbonyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (16n)
The procedure described for the synthesis of 16a was applied to
the amide intermediate (7) and cyclopropanecarbonyl chloride
providing the title product. 1H NMR (400 MHz, CDCl3) d 9.42 (br
s, 1H, –NH–), 7.44 (d, J = 1.8 Hz, 1H), 7.34–7.24 (m, 4H), 7.07 (d,
J = 8.2 Hz, 2H), 3.04–2.97 (m, 1H), 2.39 (s, 3H), 1.23–1.19 (m, 2H),
1.05–1.00 (m, 2H). MS, m/z = 448 ([M+H]+).
4.2.34. N-(tert-Butylcarbamoyl)-5-(4-chlorophenyl)-1-(2,4-
dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (17f)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and tert-butyl isocyanate providing the
title product. 1H NMR (400 MHz, CDCl3) d 8.70 (br s, 1H, –NH–,
imide), 8.36 (br s, 1H, –NH–, amide), 7.44 (d, J = 2.3 Hz, 1H),
7.33–7.23 (m, 4H), 7.06 (d, J = 8.7 Hz, 2H), 2.35 (s, 3H), 1.44 (m,
9H). MS, m/z = 479 ([M+H]+).
4.2.29. 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(hexylcar-
bamoyl)-4-methyl-1H-pyrazole-3-carboxamide (17a)
To a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-
methyl-1H-pyrazole-3-carboxamide (228 mg, 0.6 mmol) in THF
(5 mL) was added 1 M NaHMDS (0.9 mL, 0.9 mmol) at ꢀ78 °C un-
der a nitrogen atmosphere. After stirring for 20 min, hexyl isocya-
nate (76.3 mg, 0.6 mmol) dissolved in THF (1 mL) was added
4.2.35. 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-
(phenylcarbamoyl)-1H-pyrazole-3-carboxamide (17g)
The procedure described for the synthesis of 17a was applied to
the amide intermediate (7) and phenyl isocyanate providing the ti-