Water → HCID 66863502, compound

HRID 253052Notes

Reaction equation

HRID 253052 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([N:9]2[CH2:14][CH2:13][N:12]([NH:15][C:16]([C:18]3[C:22]([O:23][CH3:24])=[C:21]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=4)[N:20]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[Cl:38])[N:19]=3)=[O:17])[CH2:11][CH2:10]2)=[O:8])=[CH:4][CH:3]=1.O.C(OCC)(=O)C.[CH3:46][N:47](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:46]([C:2]1[S:6][C:5]([C:7]([N:9]2[CH2:10][CH2:11][N:12]([NH:15][C:16]([C:18]3[C:22]([O:23][CH3:24])=[C:21]([C:25]4[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=4)[N:20]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[Cl:38])[N:19]=3)=[O:17])[CH2:13][CH2:14]2)=[O:8])=[CH:4][CH:3]=1)#[N:47]

Participants

8

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 66862538HCID 66862538, compound

Product 1

HCID 66863502HCID 66863502, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
180 °C

Procedure

To a solution of the compound obtained in Example 24A (49 mg) in dimethylformamide (1 mL) was added zinc cyanide (6 mg), tris(dibenzylideneacetone)-dipalladium (1.5 mg) and 1,1′-bis(diphenylphosphino)ferrocene (DPPF, 1.8 mg) and the mixture was stirred at 180° C. for 15 minutes in a microwave reactor. After cooling to room temperature, to the reaction mixture was added water and ethyl acetate. The mixture was stirred and the organic layer was extracted by diatomaceous earth column (CHEM ELUTE, VARIAN Inc.) and the extract was concentrated in vacuo. The extract was concentrated in vacuo and the crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=30/70 to 0/100) to obtain 3-[N-[4-(5-cyano-2-thenoyl)piperazin-1-yl)carbamoyl]-1-(2-chlorophenyl)-5-(4-chloro-phenyl)-4-methoxy-1H-pyrazole (79 mg; yield: 83%) as a colorless solid.

Workup

  1. temperatureAfter cooling to room temperature, to the reaction mixture
  2. stirringThe mixture was stirred
  3. extractionthe organic layer was extracted by diatomaceous earth column (CHEM ELUTE, VARIAN Inc.)
  4. concentrationthe extract was concentrated in vacuo
  5. concentrationThe extract was concentrated in vacuo
  6. customthe crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=30/70 to 0/100)

Sources & evidence

ORD record
ord-81551dfb21e14e449d4047a0c2108b52
Source dataset
uspto-grants-2011_01
Patent number
US07872006B2

Reaction notes

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