Potassium Carbonate → 2-chloro-4'-[2-(2,6-dichloro-phenyl)-5-isopropyl-2H-pyrazol-3-ylmethoxy]-biphenyl-4-carboxylic acid

HRID 1672992

Reaction equation

Br[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]2[N:12]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21](O)([CH3:23])[CH3:22])[CH:9]=2)=[CH:4][CH:3]=1.[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[C:32]([Cl:39])[CH:31]=1)([OH:29])=[O:28].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.C1([Pd+]C2CCCCC2)CCCCC1.C(O)C>[Cl:39][C:32]1[CH:31]=[C:30]([C:27]([OH:29])=[O:28])[CH:35]=[CH:34][C:33]=1[C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]2[N:12]([C:13]3[C:14]([Cl:20])=[CH:15][CH:16]=[CH:17][C:18]=3[Cl:19])[N:11]=[C:10]([CH:21]([CH3:23])[CH3:22])[CH:9]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Into a 8 mL flask was added 256 mg (0.56 mmol) of 2-[5-(4-bromo-phenoxymethyl)-1 (2,6-dichloro-phenyl)-1H-pyrazol-3-yl]-propan-2-ol, 134 mg (0.67 mmol) of (4-carboxy-2-chlorophenyl)boronic acid, 200 mg of potassium carbonate (1.68 mmol), 10 mg (0.017 mmol) of dicyclohexyl palladium acetate and 2 mL of ethanol. The reaction mixture was heated to 80° C. for 4 h. After cooling, the crude reaction mixture was filtered through a pad of celite, concentrated in vacuo, and purified on a reverse phase HPLC-MS to afford 2-chloro-4′-[2-(2,6-dichloro-phenyl)-5-isopropyl-2H-pyrazol-3-ylmethoxy]-biphenyl-4-carboxylic acid as an off white solid (34 mg, 11%); 1H NMR (400 MHz, CDCl3): δ 8.16 (m, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.45 (d, J=7.83 Hz, 2H) 7.35 (m, 4H), 6.88 (d, J=8.84 Hz, 2H), 6.54 (s, 1H), 4.92 (s, 2H), 1.66 (s 6H), MS (ES): 531 [M+H]+.

Workup

temperatureAfter cooling
customthe crude reaction mixture
filtrationwas filtered through a pad of celite
concentrationconcentrated in vacuo
custompurified on a reverse phase HPLC-MS

Sources & evidence

ORD record: ord-61e76c2cf45d455aa32d346dc2522419
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998995B2

Linked notes

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