Acetamide → HCID 52944597, compound

HRID 1510100Notes

Reaction equation

HRID 1510100 reaction equation
C(OC(N1CCN(C([C:16]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:25]#[N:26])[CH:23]=3)[N:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:17]=2[O:33][C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[CH3:41])=O)CC1)=O)(C)(C)C.[C:42]([NH2:45])(=[O:44])C.[OH2:46]>C1COCC1.[Pd](Cl)Cl>[F:40][C:38]1[CH:37]=[CH:36][C:35]([CH3:41])=[C:34]([CH:39]=1)[O:33][C:17]1[N:18]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:19]2[C:24]([C:16]=1[C:42]([N:45]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[O:44])=[CH:23][C:22]([C:25]([NH2:26])=[O:46])=[CH:21][CH:20]=2

Participants

6

Reactant 3

HCID 178AcetamideHCID 962Water2×HCID 66920257HCID 66920257, compound

Product 1

HCID 52944597HCID 52944597, compound

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-[5-cyano-2-(5-fluoro-2-methyl-phenoxy)-1-phenyl-1H-indole-3-carbonyl]-piperazine-1-carboxylic acid tert-butyl ester (70 mg, 0.126 mmol), acetamide (31.5 mg, 0.53 mmol) and palladium(II) chloride (2.2 mg, 13 μmol) in THF (4 ml) and water (1.4 ml) was stirred at room temperature for 30 h. After addition of water, the mixture was extracted with EA. The combined organic layers were dried over sodium sulfate and concentrated. The residue was dissolved in DCM (1 ml), TFA (0.3 ml) was added, and the mixture was stirred at room temperature for 1 h. The solvents were evaporated and the obtained solid was purified by preparative HPLC. The eluate was lyophilized overnight. The residue was dissolved in a small quantity of MOH, mixed with hydrochloric acid (0.1 M) and lyophilized overnight. 13.5 mg of the title compound were obtained in the form of the 2-(5-fluoro-2-methyl-phenoxy)-1-phenyl-3-(piperazine-1-carbonyl)-1H-indole-5-carboxylic acid amide hydrochloride.

Workup

  1. extractionthe mixture was extracted with EA
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in DCM (1 ml)
  5. additionTFA (0.3 ml) was added
  6. stirringthe mixture was stirred at room temperature for 1 h
  7. customThe solvents were evaporated
  8. customthe obtained solid was purified by preparative HPLC
  9. waitThe eluate was lyophilized overnight
  10. dissolutionThe residue was dissolved in a small quantity of MOH
  11. additionmixed with hydrochloric acid (0.1 M)
  12. waitlyophilized overnight

Sources & evidence

ORD record
ord-46534b988a374f88bac8dc522681585b
Source dataset
uspto-grants-2012_07
Patent number
US08211885B2

Reaction notes

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