1462
H. K. YANG ET AL.
2.76–2.65 (m, 4H) 2.56–2.47 (m, 5H) 2.08–2.02 (m, 1H) 1.90–1.81 2.51–2.46 (m, 5H), 2.03–1.97 (m, 1H), 1.85–1.78 (m, 1H), 1.58–1.54
(m, 1H) 1.63–1.57 (m, 1H) 0.88 (d, J ¼ 6.60 Hz, 6H); 13C NMR (m, 1H), 0.84 (d, J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) d:
(75 MHz, CDCl3) d: 162.98 146.09 145.37 141.22 139.26 129.60 164.17, 162.94 (d, JC-F ¼ 245.9 Hz), 162.81 (d, JC-F ¼ 246.2 Hz),
129.34 129.11 128.88 125.90 125.77 125.67 122.27 106.4857.15 146.83, 145.03, 144.29 (d, JC-F ¼ 18.0 Hz), 144.29, 139.43, 129.23,
56.65 53.53 41.65 37.93 35.08 32.60 28.32 27.61 22.32.
128.68, 125.91, 111.42 (d, JC-F ¼ 6.4 Hz), 111.24 (d, JC-F ¼ 6.2 Hz),
106.49, 101.51 (d, JC-F ¼ 25.3 Hz), 101.25 (d, JC-F ¼ 25.1 Hz), 58.30,
56.98, 53.75, 43.88, 37.00, 35.20, 35.07, 28.32, 28.28, 22.30; HR-MS
m/z [M þ H]þ (ESIþ) calcd. for C27H33F2N4O ¼ 467.2616,
found 467.2613.
(R)-5-Isobutyl-1-phenyl-N-((1-(3-(trifluoromethyl)phenethyl)pyrroli-
din-3-yl)methy-l)-1H-pyrazole-3-carboxamide (20b)
Yield 35%; 1H NMR (300 MHz, CDCl3) d: 7.51–7.30 (m, 9H), 6.79
(s, 1H), 3.47–3.38 (m, 2H), 2.87–2.82 (m, 2H), 2.78–2.65 (m, 4H),
2.58–2.49 (m, 5H), 2.08 (s, 1H), 1.9–1.78 (m, 1H), 1.64–1.53 (m, 1H),
0.89 (d, J ¼ 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) d 162.55 146.85
145.07 141.24 139.45 132.08 130.74 130.43 129.25 128.72 128.70
125.96 125.57 125.31 125.28 122.91 122.88 58.38 57.54 53.82
43.90 37.06 35.18 35.12 28.37 28.32 22.34.
(R)-N-((1-(2,3-difluorophenethyl)pyrrolidin-3-yl)methyl)-5-isobutyl-
1-phenyl-1H-pyrazole-3-carboxamide (20g)
Yield 76%; 1H NMR (400 MHz, CDCl3) d: 7.46–7.35 (m, 6H),
6.94–6.84 (m, 3H), 6.72 (s, 1H), 3.43–3.35 (m, 2H), 2.82–2.78 (m,
2H), 2.70–2.59 (m, 4H), 2.52–2.43 (m, 5H), 2.00–1.95 (m, 1H),
1.83–1.76 (m, 1H), 1.56–1.52 (m, 1H), 0.82 (d, J ¼ 6.6 Hz, 6H); 13C
NMR (100 MHz, CDCl3) d: 162.45, 150.53 (d, JC-F ¼ 245.7 Hz),
150.40 (d, JC-F ¼ 245.6 Hz), 148.98 (d, JC-F ¼ 244.5 Hz), 148.86
(d, JC-F ¼ 244.6 Hz), 146.82, 139.40, 129.77, 129.64, 129.15, 128.56,
125.83, 125.44 (d, JC-F ¼ 3.6 Hz), 125.40 (d, JC-F ¼ 3.5 Hz), 123.70
(d, JC-F ¼ 6.8 Hz), 123.66 (d, JC-F ¼ 6.9 Hz), 114.84 (d, JC-F ¼ 16.9 Hz),
106.45, 58.20, 55.94, 53.68, 43.85, 37.04, 35.03, 28.50, 28.30,
28.23, 22.24; HR-MS m/z [M þ H]þ (ESIþ) calcd. for
C27H33F2N4O ¼ 467.2616, found 467.2609.
(R)-5-Isobutyl-1-phenyl-N-((1-(2-(trifluoromethyl)phenethyl)pyrroli-
din-3-yl)methy-l)-1H-pyrazole-3-carboxamide (20c)
Yield 27%; 1H NMR (300 MHz, CDCl3) d: 7.58–7.24 (m, 9H), 6.75
(s, 1H), 3.46–3.43 (m, 2H), 2.97–2.94 (m, 2H), 2.78–2.46 (m, 9H),
2.18–1.99 (m, 1H), 1.88–1.78 (m, 1H), 1.63–1.55 (m, 1H), 0.87
(d, J ¼ 6.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) d: 162.54 146.82
145.08 139.43 138.89 131.72 131.59 129.27 128.80 128.69 128.41
126.37 126.13 125.97 125.89 125.82 125.74 122.74 106.53 58.24
57.74 53.68 43.85 37.14 35.12 32.10 28.41 28.33 22.35.
(R)-N-((1-(3-chloro-5-fluorophenethyl)pyrrolidin-3-yl)methyl)-5-iso-
butyl-1-phenyl-1H-pyrazole-3-carboxamide (20h)
Yield 71%; 1H NMR (400 MHz, CDCl3) d: 7.55 (t, J ¼ 5.5 Hz, 1H),
7.50–7.39 (m, 5H), 6.90–6.87 (m, 2H), 6.77 (s, 1H), 6.73
(d, J ¼ 9.2 Hz, 1H), 3.49–3.37 (m, 2H), 2.76–2.60 (m, 6H), 2.52–2.46
(m, 5H), 2.06–1.98 (m, 1H), 1.89–1.79 (m, 1H), 1.62–1.54 (m, 1H),
0.86 (d, J ¼ 6.6 Hz, 6H); 13C NMR (100 MHz, CDCl3) d: 162.56
(d, JC-F ¼ 247.2 Hz), 162.51, 146.88, 144.99, 144.21 (d, JC-F ¼ 8.2 Hz),
139.45, 134.53 (d, JC-F ¼ 10.8 Hz), 129.21, 128.66, 125.90, 124.62
(d, JC-F ¼ 2.8 Hz), 113.99 (d, JC-F ¼ 21.2 Hz), 113.76 (d, JC-F ¼ 25.3 Hz),
106.48, 58.38, 57.00, 53.76, 43.96, 36.96, 35.08, 28.34, 28.28, 22.29;
HR-MS m/z [M þ H]þ (ESIþ) calcd. for C27H33ClFN4O ¼ 483.2321,
found 483.2316.
(R)-N-((1-(3-fluorophenethyl)pyrrolidin-3-yl)methyl)-5-isobutyl-1-
phenyl-1H-pyrazole-3-carboxamide (20d)
Yield 70%; 1H NMR (400 MHz, CDCl3) d: 7.49–7.38 (m, 6H),
7.20–7.15 (m, 1H), 6.90–6.81 (m, 3H), 6.76 (s, 1H), 3.47–3.39
(m, 2H), 2.79–2.61 (m, 6H), 2.54–2.45 (m, 5H), 2.04–1.98 (m, 1H),
1.86–1.79 (m, 1H), 1.61–1.54 (m, 1H), 0.85 (d, J ¼ 6.6 Hz, 6H); 13C
NMR (100 MHz, CDCl3) d: 162.78 (d, JC-F ¼ 243.7 Hz), 162.50, 146.86,
144.97, 142.97 (d, JC-F ¼ 7.2 Hz), 139.43, 129.63 (d, JC-F ¼ 8.2 Hz),
129.21, 128.63, 125.88, 124.23 (d, JC-F ¼ 2.7 Hz), 115.39
(d, JC-F ¼ 20.8 Hz), 112.76 (d, JC-F ¼ 20.9 Hz), 106.50, 58.34, 57.49,
53.82, 43.92, 37.01, 35.28, 35.07, 28.34, 28.26, 22.29; HR-MS m/z
[M þ H]þ (ESIþ) calcd. for C27H34FN4O ¼ 449.2711, found 449.2707.
(R)-N-((1-(4-chloro-3-fluorophenethyl)pyrrolidin-3-yl)methyl)-5-iso-
butyl-1-phenyl-1H-pyrazole-3-carboxamide (20i)
(R)-N-((1-(3,4-difluorophenethyl)pyrrolidin-3-yl)methyl)-5-isobutyl-
1-phenyl-1H-p-yrazole-3-carboxamide (20e)
Yield 75%; H NMR (400 MHz, CDCl3) d: 7.47–7.37 (m, 6H), 7.01–6.94
(m, 1H), 6.92–6.87 (m, 1H), 6.81–6.79 (br m, 1H), 6.75 (s, 1H),
3.43–3.38 (m, 2H), 2.73–2.58 (m, 6H), 2.51–2.43 (m, 5H), 2.04–1.95
(m, 1H), 1.85–1.78 (m, 1H), 1.59–1.51 (m, 1H), 0.84 (d, J ¼ 6.6 Hz, 6H);
13C NMR (100 MHz, CDCl3) d: 162.49, 150.05 (d, JC-F ¼ 245.6 Hz),
149.92 (d, JC-F ¼ 245.7 Hz), 148.79 (d, JC-F ¼ 244.1 Hz), 148.66
(d, JC-F ¼ 244.1 Hz), 146.84, 144.98, 139.42, 137.41 (d, JC-F ¼ 4.2 Hz),
137.35 (d, JC-F ¼ 4.0 Hz), 129.19, 128.62, 125.87, 124.39
Yield 77%; 1H NMR (400 MHz, CDCl3) d: 7.50 (t, J ¼ 5.5 Hz, 1H),
7.45–7.35 (m, 5H), 7.18 (t, J ¼ 7.9 Hz, 1H), 6.85 (dd, J ¼ 10.1, 1.7 Hz,
1H), 6.79 (d, J ¼ 8.0 Hz, 1H), 6.73 (s, 1H), 3.43–3.34 (m, 2H),
2.72–2.56 (m, 6H), 2.48–2.42 (m, 5H), 2.01–1.92 (m, 1H), 1.83–1.76
(m, 1H), 1.57–1.49 (m, 1H), 0.82 (d, J ¼ 6.6 Hz, 6H); 13C NMR
(100 MHz, CDCl3) d: 162.47, 157.76 (d, JC-F ¼ 246.7 Hz), 146.83,
144.93, 141.50, 141.44, 139.41, 130.12, 129.17, 128.60, 125.83,
125.04 (d, JC-F ¼ 3.3 Hz), 118.08 (d, JC-F ¼ 17.5 Hz), 116.63
(d, JC-F ¼ 20.4 Hz), 106.46, 58.27, 57.14, 53.74, 43.89, 36.96, 35.03,
1
(d, JC-F ¼ 3.5 Hz), 124.33 (d, JC-F ¼ 3.5 Hz), 117.23 (d, JC-F ¼ 16.7 Hz), 34.77, 28.28, 28.23, 22.25; HR-MS m/z [M þ H]þ (ESIþ) calcd. for
116.80 (d, JC-F ¼ 16.8 Hz), 106.47, 58.28, 57.43, 53.76, 43.88, 36.99, C27H33ClFN4O ¼ 483.2321, found 483.2316.
35.04, 34.64, 28.29, 28.25, 22.26; HR-MS m/z [M þ H]þ (ESIþ) calcd. for
C27H33F2N4O¼ 467.2616, found 467.2612.
(R)-N-((1-(3,4-dichlorophenethyl)pyrrolidin-3-yl)methyl)-5-isobutyl-
1-phenyl-1H-pyrazole-3-carboxamide (20j)
Yield 77%; 1H NMR (400 MHz, CDCl3) d: 7.50 (t, J ¼ 5.5 Hz, 1H)
(R)-N-((1-(3,5-difluorophenethyl)pyrrolidin-3-yl)methyl)-5-isobutyl-
1-phenyl-1H-pyrazole-3-carboxamide (20f)
7.47–7.36 (m, 5H), 7.25 (d, J ¼ 8.2 Hz, 1H), 7.17 (d, J ¼ 1.9. Hz, 1H),
Yield 70%; 1H NMR (400 MHz, CDCl3) d: 7.51–7.37 (m, 6H), 6.75 6.92 (dd, J ¼ 8.2, 2.0 Hz, 1H), 6.74 (s, 1H), 3.45–3.35 (m, 2H),
(s, 1H), 6.64–6.55 (m, 3H), 3.46–3.39 (m, 2H), 2.76–2.59 (m, 6H), 2.71–2.56 (m, 6H), 2.49–2.43 (m, 5H), 2.02–1.94 (m, 1H), 1.84–1.77