Imidazole → 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-(1H-imidazol-1-yl)benzoic acid

HRID 915591Notes

Reaction equation

[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:20]=[C:19](F)[CH:18]=[CH:17][C:12]=2[C:13]([O:15]C)=[O:14])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:20]=[C:19]([N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)[CH:18]=[CH:17][C:12]=2[C:13]([OH:15])=[O:14])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])[N:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

Conditions

Temperature: 110 °C

Procedure

To a mixture of methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-fluorobenzoate (Example 246, 50 mg, 0.13 mmol), imidazole (17.8 mg, 0.26 mmol), and potassium carbonate (90.6 mg, 0.66 mmol) was added DMF (1 mL). The mixture was then heated to 110° C. for 16 h. The reaction mixture was allowed to cool to rt. The solvent was removed under reduced pressure, and the crude was purified by HPLC purification using gradient elution from 10 to 80% acetonitrile in water to afford 13.8 mg (25%) of the title compound. 1H NMR (300 MHz, CD3OD) δ 9.48 (t, 1H), 8.15 (d, 1H), 8.07 (t, 1H), 7.76 (t, 1H), 7.52 (d, 1H), 7.28-7.42 (m, 4H), 7.10 (dd, 1H), 6.48 (s, 1H), 2.06 (s, 3H), 1.35 (s, 9H). ES-MS m/z 416.2 (MH+); HPLC RT (min) 2.21.

Workup

temperatureto cool to rt
customThe solvent was removed under reduced pressure
customthe crude was purified by HPLC purification
washelution from 10 to 80% acetonitrile in water

Sources & evidence

ORD record: ord-bd69c120d4324726b2a12c365dad9595
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07265144B2

Reaction notes

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