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117.38 (t, JCF ¼ 258.56 Hz), 96.89, 64.30, 52.49, 49.23, 45.19, 28.62,
24.99, 23.57. C20H25F2N5O Mass (calculated): 405.45; (found): 406
[Mþ1]. HPLC (10 min method); Rt ¼ 1.71; area 100%.
7.2.5.17. 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [5-(5-chloro-
2-methyl-phenyl)-2H-pyrazol-3-yl]-amide (26k). Following the
general procedure for urea synthesis and starting from amino-
pyrazole 23c and amine 25c, 44 mg of compound 26k were ob-
tained as formate salt after preparative HPLC (52% yield). 1H NMR
7.2.5.13. 3-Piperidin-1-yl-pyrrolidine-1-carboxylic acid [5-(5-chloro-
2-methyl-phenyl)-2H-pyrazol-3-yl]-amide (26g). Following the
general procedure for urea synthesis and starting from amino-
pyrazole 23c and amine 25b, 64 mg of compound 26g were ob-
tained as formate salt after preparative HPLC (75% yield). 1H NMR
(400 MHz, DMSO-d6) d 12.19 (s, 1H), 9.15 (s, 1H), 8.14 (s, 1H), 7.48 (s,
1H), 7.30 (s, 2H), 6.42 (s, 1H), 4.16e3.97 (m, 2H), 2.91e2.75 (m, 6H),
2.72e2.55 (m, 1H), 2.35 (s, 3H), 1.96e1.82 (m, 2H), 1.82e1.67 (m,
4H),1.44e1.26 (m, 2H). 13C NMR (101 MHz, CD3OD)
d 168.73,155.54,
146.58, 143.87, 134.84, 132.62, 132.23, 131.38, 128.39, 128.09,
96.97.62.12, 51.49, 42.52, 28.71, 22.68, 19.16. C20H26ClN5O Mass
(calculated): 387.92; (found): 388 [Mþ1; Cl pattern]. HPLC (10 min
method); Rt ¼ 1.74; area 100%.
(400 MHz, DMSO-d6) d 12.21 (s,1H), 8.82 (s,1H), 8.11 (s,1H), 7.48 (s,
1H), 7.31 (s, 2H), 6.45 (s, 1H), 3.91e3.68 (m, 1H), 3.63e3.48 (m, 1H),
3.40e3.21 (m, 4H), 2.68 (d, J ¼ 30.8 Hz, 3H), 2.35 (s, 3H), 2.26e2.07
(m, 1H), 1.98e1.75 (m, 1H), 1.68e1.51 (m, 4H), 1.51e1.33 (m, 2H). 13
C
NMR (101 MHz, CD3OD)
d 167.58, 154.64, 146.25, 143.79, 134.83,
132.58, 132.25, 131.38, 128.37, 128.09, 96.86, 64.00, 52.33, 47.29,
44.36, 27.27, 23.43, 21.80, 19.19. C20H26ClN5O Mass (calculated):
387.92; (found): 388 [Mþ1; Cl pattern]. HPLC (10 min method);
Rt ¼ 1.78; area 100%.
7.2.5.18. 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [5-(4-chloro-
2-methyl-phenyl)-2H-pyrazol-3-yl]-amide (26l). Following the
general procedure for urea synthesis and starting from amino-
pyrazole 23d and amine 25c, 53 mg of compound 26l were ob-
tained (62% yield). 1H NMR (400 MHz, DMSO-d6)
d 12.27 (s, 1H),
9.16 (s,1H), 7.65e7.10 (m, 3H), 6.41 (s,1H), 4.23e4.08 (m, 2H), 3.24e
2.87 (m, 5H), 2.83e2.68 (m, 2H), 2.36 (s, 3H), 2.07e1.90 (m, 2H),
1.91e1.71 (m, 4H), 1.53e1.30 (m, 2H). 13C NMR (101 MHz,
7.2.5.14. 3-Piperidin-1-yl-pyrrolidine-1-carboxylic acid [5-(4-chloro-
2-methyl-phenyl)-2H-pyrazol-3-yl]-amide (26h). Following the
general procedure for urea synthesis and starting from amino-
pyrazole 23d and amine 25b, 49 mg of compound 26h were ob-
tained as formate salt after preparative HPLC (57% yield). 1H NMR
CD3OD þ formic acid)
d 163.34, 156.63, 148.09, 144.80, 139.55,
135.28, 131.59, 131.47, 127.13, 98.23, 63.31, 52.82, 43.64, 29.82,
23.83, 20.66. C20H26ClN5O Mass (calculated): 387.92; (found): 388
(Mþ1; Cl pattern). HPLC (10 min method); Rt ¼ 1.83; area 100%.
(400 MHz, DMSO-d6) d 12.13 (s,1H), 8.75 (s,1H), 8.11 (s,1H), 7.43 (d,
J ¼ 8.3 Hz, 1H), 7.40e7.35 (m, 1H), 7.30 (d, J ¼ 8.3 Hz, 1H), 6.39 (s,
1H), 3.75e3.64 (m, 1H), 3.59e3.47 (m, 1H), 3.30e3.20 (m, 4H),
3.20e3.06 (m, 4H), 3.06e2.86 (m, 1H), 2.70e2.53 (m, 1H), 2.36 (s,
3H), 2.20e2.02 (m, 1H), 1.83e1.66 (m, 1H), 1.63e1.46 (m, 4H), 1.46e
7.2.5.19. [1,40]Bipiperidinyl-10-carboxylic
acid
[5-(4-methoxy-
phenyl)-2H-pyrazol-3-yl]-amide, formate salt (26m). Following the
general procedure for urea synthesis and starting from amino-
pyrazole 23a and amine 25d, 63 mg of compound 26m were ob-
1.28 (m, 2H). 13C NMR (101 MHz, CD3OD)
d 167.56, 154.74, 146.62,
149.68, 138.34, 133.99, 130.39, 130.29, 129.47, 125.92, 96.98, 64.09,
52.41, 48.24, 44.39, 27.55, 23.72, 20.09, 19.50. C20H26ClN5O Mass
(calculated): 387.92; (found): 388 [Mþ1; Cl pattern]. HPLC (10 min
method); Rt ¼ 1.76; area 100%.
tained (74% yield). 1H NMR (400 MHz, DMSO-d6)
d 9.07 (s, 1H),
7.69e7.43 (m, 2H), 7.03e6.88 (m, 2H), 6.51 (s, 1H), 4.23 (d,
J ¼ 13.7 Hz, 2H), 3.76 (s, 3H), 3.11e2.82 (m, 5H), 2.82e2.68 (m, 2H),
1.90 (d, J ¼ 9.7 Hz, 2H), 1.63 (s, 4H), 1.44 (d, J ¼ 12.1 Hz, 4H). 13C NMR
(101 MHz, CD3OD)
d 169.73, 161.33, 156.74, 148.64, 146.28, 127.77,
7.2.5.15. 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [5-(4-
methoxy-phenyl)-2H-pyrazol-3-yl]-amide, formate salt (26i).
Following the general procedure for urea synthesis and starting
from aminopyrazole 23a and amine 25c, 73 mg of compound 26i
were obtained (89% yield). Mass (calculated) (found): 370 [Mþ1].
HPLC (10 min method); Rt ¼ 1.36; area 99%. 1H NMR (400 MHz,
124.31, 115.34, 94.50, 64.96, 55.79, 51.18, 43.95, 27.52, 24.54, 22.97.
C
21H29N5O2 Mass (calculated): 383.50; (found): 384 [Mþ1]. HPLC
(10 min method); Rt ¼ 1.49; area 97%.
7.2.5.20. [1,40]Bipiperidinyl-10-carboxylic acid [5-(2-difluoromethoxy-
phenyl)-2H-pyrazol-3-yl]-amide (26n). Following the general pro-
cedure for urea synthesis and starting from aminopyrazole 23b and
amine 25d, 47 mg of compound 26n were obtained as formate salt
DMSO-d6)
d 12.78e11.07 (m, 1H), 9.06 (s, 1H), 7.77e7.45 (m, 2H),
7.13e6.87 (m, 2H), 6.51 (s, 1H), 4.29e4.00 (m, 2H), 3.76 (s, 3H),
3.11e2.93 (m, 4H), 2.91e2.83 (m, 1H), 2.83e2.68 (m, 2H), 1.95 (d,
J ¼ 10.2 Hz, 2H),1.85 (d, J ¼ 29.9 Hz, 4H),1.57e1.26 (m, 2H). 13C NMR
(50% yield). 1H NMR (400 MHz, DMSO-d6)
d 12.22 (brs, 1H), 9.10 (s,
(101 MHz, DMSO-d6, VT ¼ 60 ꢀC)
d
158.89, 154.28, 147.24, 143.32,
1H), 8.13 (s, 1H), 7.87e7.61 (m, 1H), 7.38 (t, J ¼ 7.9 Hz, 1H), 7.33e7.25
(m, 2H), 7.24 (t, J ¼ 73.6 Hz, 1H), 6.60 (s, 1H), 4.27e4.12 (m, 2H),
2.84e2.57 (m, 7H), 1.84e1.70 (m, 2H), 1.61e1.47 (m, 4H), 1.47e1.29
126.12, 123.43, 114.18, 92.47, 60.81, 55.09, 50.64, 42.15, 28.83,
22.53.C20H27N5O2 Mass (calculated): 369.42; (found): 370 [Mþ1].
HPLC (10 min method); Rt ¼ 1.36; area 99%.
(m, 4H). 13C NMR (101 MHz, CD3OD)
d 168.72, 155.58, 148.35, 146.71,
140.65, 129.54, 128.78, 125.54, 122.72, 119.31, 116.84 (t,
1JCF ¼ 259.57 Hz), 97.19, 63.75, 49.98, 42.62, 26.37, 23.42, 21.88.
7.2.5.16. 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [5-(2-
difluoromethoxy-phenyl)-2H-pyrazol-3-yl]-amide, formate salt (26j).
Following the general procedure for urea synthesis and starting
from aminopyrazole 23b and amine 25c, 73 mg of compound 26j
were obtained as formate salt after preparative HPLC (81% yield). 1H
C
21H27F2N5O2 Mass (calculated): 419.48; (found): 420 [Mþ1]. HPLC
(10 min method); Rt ¼ 1.61; area 99%.
7.2.5.21. [1,40]Bipiperidinyl-10-carboxylic acid [5-(5-chloro-2-methyl-
phenyl)-2H-pyrazol-3-yl]-amide (26o). Following the general pro-
cedure for urea synthesis and starting from aminopyrazole 23c and
amine 25d, 47 mg of compound 26o were obtained as formate salt
after preparative HPLC (56% yield). 1H NMR (400 MHz, DMSO-d6)
NMR (400 MHz, DMSO-d6) d 12.04 (bs, 1H), 9.13 (s, 1H), 8.13 (s, 1H),
7.80 (d, J ¼ 7.1 Hz, 1H), 7.42e7.35 (m, 1H), 7.33e7.25 (m, 2H), 7.24 (t,
J ¼ 74.0 Hz, 1H), 6.61 (s, 1H), 4.09 (d, J ¼ 13.6 Hz, 2H), 2.96e2.74 (m,
6H), 2.74e2.58 (m, 1H), 2.00e1.84 (m, 2H), 1.83e1.68 (m, 4H), 1.48e
1.28 (m, 2H). 13C NMR (101 MHz, DMSO-d6, VT ¼ 60 ꢀC)
d
164.28,
d 11.95 (s, 1H), 9.15 (s, 1H), 8.15 (s, 1H), 7.47 (s, 1H), 7.37e7.22 (m,
154.39, 147.49, 146.02, 140.00, 129.15, 128.51, 125.50, 119.33, 119.19,
116.62, 114.05, 96.36, 60.83, 50.72, 42.33, 29.43, 22.75.
2H), 6.42 (s, 1H), 4.25e4.12 (m, 2H), 2.87e2.63 (m, 7H), 2.35 (s, 3H),
1.90e1.74 (m, 2H), 1.64e1.48 (m, 4H), 1.48e1.30 (m, 4H). 13C NMR
C
20H25F2N5O2 Mass (calculated): 405.45; (found): 406 [Mþ1]. HPLC
(101 MHz, CD3OD)
132.23, 131.38, 128.39, 128.09, 96.95, 63.74, 49.97, 42.81, 26.35,
d 168.63, 155.50, 146.64, 143.68, 134.84, 132.60,
(10 min method); Rt ¼ 1.53; area 100%.