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

HRID 1672994

Reaktionsgleichung

Reaktionsgleichung von HRID 1672994
Br[C:2]1[CH:25]=[CH:24][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]([CH:21]([CH3:23])[CH3:22])[CH:9]=2)=[CH:4][CH:3]=1.[C:26]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[C:31]([Cl:38])[CH:30]=1)([OH:28])=[O:27].C(=O)([O-])[O-].[K+].[K+]>[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].COCCOC.O>[Cl:38][C:31]1[CH:30]=[C:29]([C:26]([OH:28])=[O:27])[CH:34]=[CH:33][C:32]=1[C:2]1[CH:25]=[CH:24][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]([CH:21]([CH3:23])[CH3:22])[CH:9]=2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 17750227SimtuzumabHCID 592401025-(4-bromophenoxymethyl)-1-(2,6-dichlorophenyl)-3-isopropyl-1H-pyrazole

Produkt 1

HCID 592401012-chloro-4'-[2-(2,6-dichloro-phenyl)-5-isopropyl-2H-pyrazol-3-ylmethoxy]-biphenyl-4-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178506421HCID 178506421, VerbindungKatalysatorHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Into a 8 mL flask was added 200 mg (0.454 mmol) of 5-(4-bromophenoxymethyl)-1-(2,6-dichlorophenyl)-3-isopropyl-1H-pyrazole, 108 mg (0.54 mmol) of (4-carboxy-2-chlorophenyl)boronic acid, 186 mg of potassium carbonate (1.36 mmol) and 2 mL of 9:1 DME-water. The solution was sparged under argon and 6.5 mg (0.01 mmol) of palladium dppf was added. The reaction mixture was heated to 80° C. for 4 h. After cooling, the crude reaction was filtered through a pad of celite, concentrated in vacuo, and purified directly on a reverse phase HPLC-MS to afford 2-chloro-4′-[2-(2,6-dichlorophenyl)-5-isopropyl-2H-pyrazol-3-ylmethoxy]-biphenyl-4-carboxylic acid as an off white solid, yield (80.1 mg, 34%); 1H NMR (400 MHz, DMSO-d6): δ 13.37 (s, 1H), 8.04 (m, 1H), 7.96 (dd, J=8.1 (1.77) Hz, 1H), 7.73 (d J=8.1 Hz, 2H) 7.61 (m, 1H), 7.55 (d, J=7.83 Hz, 1H), 7.41 (d, J=8.84 Hz, 2H), 6.98 (d, J=9.09 Hz, 2H), 6.61 (s, 1H), 5.01 (s, 1H), 4.83 (s, 2H), 3.02 (m 1H), 2.52 (s, 1H), 1.31 (d J=6.82 Hz 6H), MS (ES): 515 [M+H]+.

Aufarbeitung

  1. customThe solution was sparged under argon
  2. temperatureAfter cooling
  3. customthe crude reaction
  4. filtrationwas filtered through a pad of celite
  5. concentrationconcentrated in vacuo
  6. custompurified directly on a reverse phase HPLC-MS

Quellen und Nachweise

ORD-Eintrag
ord-743fb86cd8c34fd9aead915bce12a777
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07998995B2

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