Full Papers
4’-[(3-{[3-(2,6-Dichlorophenyl)-5-propylisoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl}biphenyl-2-carboxylic acid (5c): Com-
pound 5c was prepared from 19a in the same manner as that de-
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.94 (d, J=7.7 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.48–7.40 (m, 2H),
7.36 (t, J=7.0 Hz, 3H), 7.34–7.28 (m, 3H), 7.15 (d, J=7.4 Hz, 2H),
7.08 (s, 1H), 5.51 (s, 1H), 5.05 (s, 2H), 4.94 (s, 2H), 2.88 (t, J=7.2 Hz,
3H), 1.80 (dd, J=14.5, 7.2 Hz, 2H), 0.98 ppm (t, J=7.2 Hz, 3H).
HRMS (ESI): m/z: calcd for C30H5Cl2N3NaO4 [M+Na]+ 584.1120;
found: 584.1111. Purity (HPLC): 96%.
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.97–7.88 (m, 3H), 7.56 (t, J=7.8 Hz, 1H), 7.49 (s, 3H), 7.45 (d, J=
8.1 Hz, 1H), 7.39 (d, J=7.5 Hz, 2H), 7.31 (t, J=7.8 Hz, 4H), 7.17 (d,
J=6.8 Hz, 2H), 7.08 (s, 1H), 5.53 (s, 1H), 5.13 (s, 2H), 5.07 ppm (s,
2H). HRMS (ESI): m/z: calcd for C33H23Cl2N3NaO4 [M+Na]+
618.0963; found: 618.0954. Purity (HPLC): 95%.
4’-[(3-{[3-(2,6-Dibromophenyl)-5-methylisoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5j): Com-
pound 5j was prepared from 19b in the same manner as that de-
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.94 (d, J=7.3 Hz, 1H), 7.68–7.53 (m, 3H), 7.44 (t, J=7.1 Hz, 1H),
7.38–7.29 (m, 3H), 7.14 (d, J=3.8 Hz, 4H), 5.55 (s, 1H), 5.09 (s, 2H),
4.96 (d, J=14.6 Hz, 2H), 2.53 ppm (d, J=24.1 Hz, 3H). HRMS (EI):
m/z: calcd for C28H21Br2N3O4 [M+] 620.9899; found: 620.9896. Purity
(HPLC): 99%.
4’-[(3-{[5-tert-Butyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5d): Com-
pound 5d was prepared from 19a in the same manner as that de-
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.93 (d, J=7.3 Hz, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.44 (t, J=6.9 Hz,
1H), 7.40–7.27 (m, 5H), 7.14 (d, J=7.2 Hz, 2H), 7.02 (s, 1H), 5.50 (s,
1H), 4.98 (s, 2H), 4.94 (s, 2H), 1.50 ppm (s, 9H). HRMS (ESI): m/z:
calcd for C31H28Cl2N3O4 [M+H]+ 576.1457; found: 576.1454. Purity
(HPLC): 95%.
4’-[(3-{[3-(2,6-Difluorophenyl)-5-methylisoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5k): Com-
pound 5k was prepared from 19c in the same manner as that de-
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.95 (d, J=7.3 Hz, 1H), 7.56 (d, J=7.1 Hz, 1H), 7.48–7.29 (m, 6H),
7.17 (s, 3H), 7.00 (s, 2H), 5.53 (s, 1H), 5.12 (s, 2H), 5.03 (s, 2H),
2.53 ppm (d, J=18.6 Hz, 3H). HRMS (EI): m/z: calcd for
C28H21F2N3O4 [M+] 501.1500; found: 501.1501. Purity (HPLC): 98%.
4’-[(3-{[5-Cyclobutyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5e):
Compound 5e was prepared from 19a in the same manner as
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that described for the preparation of 5a. H NMR (400 MHz, CDCl3):
d=7.94 (d, J=7.4 Hz, 1H), 7.57 (t, J=7.5 Hz, 1H), 7.44 (t, J=7.5 Hz,
1H), 7.37 (d, J=8.0 Hz, 3H), 7.34–7.27 (m, 3H), 7.16 (d, J=6.9 Hz,
2H), 7.09 (s, 4H), 5.51 (s, 1H), 5.07 (s, 2H), 4.91 (s, 2H), 3.93–3.83
(m, 1H), 2.62–2.48 (m, 2H), 2.35 (dd, J=17.9, 10.4 Hz, 2H),
1.83 ppm (dd, J=13.7, 8.2 Hz, 2H). HRMS (ESI): m/z: calcd for
C31H26Cl2N3O4 [M+H]+ 574.1300; found: 574.1298. Purity (HPLC):
95%.
4’-[(3-{[3-(2,6-Dimethylphenyl)-5-methylisoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5l): Com-
pound 5l was prepared from 19d in the same manner as that de-
scribed for the preparation of 5a. 1H NMR (400 MHz, CDCl3): d=
7.86 (d, J=7.9 Hz, 1H), 7.49 (t, J=7.2 Hz, 1H), 7.37 (t, J=7.3 Hz,
1H), 7.26 (d, J=6.8 Hz, 3H), 7.18–7.06 (m, 3H), 7.05 (s, 1H), 6.99 (d,
J=7.4 Hz, 2H), 5.45 (s, 1H), 5.04 (s, 2H), 4.76 (s, 2H), 2.45 (d, J=
6.5 Hz, 3H), 2.02 ppm (s, 6H). HRMS (EI): m/z: calcd for C30H27N3O4
[M+] 493.2002; found: 493.2011. Purity (HPLC): 96%.
4’-[(3-{[5-Cyclopentyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5 f):
Compound 5 f was prepared from 19a in the same manner as that
4’-({3-[(5-Methyl-3-phenylisoxazol-4-yl)methoxy]-1H-pyrazol-1-
yl}methyl)biphenyl-2-carboxylic acid (5m): Compound 5m was
prepared from 19e in the same manner as that described for the
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described for the preparation of 5a. H NMR (400 MHz, CDCl3): d=
7.94 (d, J=7.7 Hz, 1H), 7.56 (t, J=7.5 Hz, 1H), 7.44 (t, J=7.3 Hz,
1H), 7.37 (d, J=8.3 Hz, 3H), 7.30 (t, J=7.7 Hz, 3H), 7.15 (d, J=
7.4 Hz, 2H), 7.07 (s, 1H), 5.51 (s, 1H), 5.02 (s, 2H), 4.92 (s, 2H), 3.45
(dd, J=14.9, 7.2 Hz, 1H), 2.00–1.81 (m, 5H), 1.75–1.62 (m, 2H),
1.32–1.19 ppm (m, 2H). HRMS (ESI): m/z: calcd for C32H28Cl2N3O4
[M+H]+ 588.1457; found: 588.1452. Purity (HPLC): 96%.
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preparation of 5a. H NMR (400 MHz, CDCl3): d=7.92 (d, J=7.6 Hz,
1H), 7.76 (s, 2H), 7.55 (t, J=7.3 Hz, 1H), 7.43 (s, 4H), 7.33 (d, J=
7.1 Hz, 3H), 7.19 (s, 3H), 5.68 (s, 1H), 5.06 (d, J=26.9 Hz, 4H),
2.47 ppm (d, J=12.2 Hz, 3H). HRMS (EI): m/z: calcd for C28H23N3O4
[M+] 465.1689; found: 465.1688. Purity (HPLC): 99%.
4’-[(3-{[3-(2,6-Dichlorophenyl)-5-(furan-2-yl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5g):
Compound 5g was prepared from 19a in the same manner as
4’-[(3-{[3-(2-Chlorophenyl)-5-methylisoxazol-4-yl]methoxy}-1H-
pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5n): Compound
5n was prepared from 19 f in the same manner as that described
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that described for the preparation of 5a. H NMR (400 MHz, CDCl3):
for the preparation of 5a. H NMR (400 MHz, CDCl3): d=7.92 (d, J=
d=7.95 (d, J=8.1 Hz, 1H), 7.63–7.53 (m, 2H), 7.48–7.41 (m, 1H),
7.39 (d, J=6.8 Hz, 2H), 7.33 (dd, J=11.2, 7.3 Hz, 3H), 7.18 (d, J=
5.1 Hz, 2H), 7.09 (d, J=10.7 Hz, 2H), 6.57 (s, 1H), 5.51 (s, 1H), 5.26
(s, 2H), 5.11 ppm (s, 2H). HRMS (ESI): m/z: calcd for C31H22Cl2N3O5
[M+H]+ 586.0937; found: 586.0934. Purity (HPLC): 97%.
7.7 Hz, 1H), 7.56 (t, J=7.0 Hz, 1H), 7.44 (t, J=8.6 Hz, 2H), 7.32 (d,
J=14.9 Hz, 4H), 7.27 (d, J=8.3 Hz, 3H), 7.12 (s, 3H), 5.53 (s, 1H),
5.06 (s, 2H), 4.99 (s, 2H), 2.48 ppm (d, J=17.1 Hz, 3H). HRMS (EI):
m/z: calcd for C28H22ClN3O4 [M+] 499.1299; found: 499.1297. Purity
(HPLC): 99%.
4’-[(3-{[3-(2,6-Dichlorophenyl)-5-(2-thienyl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5h):
Compound 5h was prepared from 19a in the same manner as
4’-[(3-{[3-(2,6-Dibromophenyl)-5-(2-thienyl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5o):
Compound 5o was prepared from 19b in the same manner as
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that described for the preparation of 5a. H NMR (400 MHz, CDCl3):
that described for the preparation of 5a. H NMR (400 MHz, CDCl3):
d=7.95 (d, J=7.0 Hz, 2H), 7.75 (s, 1H), 7.61–7.53 (m, 3H), 7.48–
7.41 (m, 3H), 7.34 (d, J=7.6 Hz, 4H), 7.19 (s, 2H), 5.58 (s, 1H),
5.15 ppm (s, 4H). HRMS (ESI): m/z: calcd for C31H22Cl2N3O4S [M+
H]+ 602.0708; found: 602.0699. Purity (HPLC): 98%.
d=7.94 (d, J=6.6 Hz, 1H), 7.72 (d, J=16.8 Hz, 1H), 7.62 (s, 2H),
7.55 (d, J=7.4 Hz, 2H), 7.44 (s, 1H), 7.31 (s, 4H), 7.17 (s, 5H), 5.59
(s, 1H), 5.10 ppm (s, 4H). HRMS (ESI): m/z: calcd for
C31H21Br2N3NaO4S [M+Na]+ 711.9717; found: 711.9510. Purity
(HPLC): 95%.
4’-[(3-{[3-(2,6-Dichlorophenyl)-5-phenylisoxazol-4-yl]methoxy}-
1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5i): Com-
pound 5i was prepared from 27i in the same manner as that de-
4’-[(3-{[3-(2,6-Difluorophenyl)-5-(2-thienyl)isoxazol-4-yl]me-
thoxy}-1H-pyrazol-1-yl)methyl]biphenyl-2-carboxylic acid (5p):
ChemMedChem 2015, 10, 1184 – 1199
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