Water → HCID 19435012, compound

HRID 1736165Notes

Reaction equation

HRID 1736165 reaction equation
Br[C:2]1[C:26]([F:27])=[C:25]([NH:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31])[C:5]2[C:6](=[O:24])[CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[C:12]([F:23])[CH:11]=3)[O:9][C:4]=2[C:3]=1[F:35].[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.O>CS(C)=O>[F:27][C:26]1[C:2]([N:40]2[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]2)=[C:3]([F:35])[C:4]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:22])[C:18]([CH3:20])([CH3:21])[CH3:19])=[C:12]([F:23])[CH:11]=3)=[CH:7][C:6](=[O:24])[C:5]=2[C:25]=1[NH:28][C:29](=[O:34])[C:30]([CH3:33])([CH3:32])[CH3:31]

Participants

5

Reactant 3

HCID 962WaterHCID 531671-MethylpiperazineHCID 10578638HCID 10578638, compound

Product 1

HCID 19435012HCID 19435012, compoundYield 58.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

580 mg (1.05 mmol) of 7-bromo-6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-pivaloylamino-4H-1-benzopyran-4-one obtained in Example 84 (2) was dissolved in 6 mL of dimethyl sulfoxide, 1.2 mL (10.5 mmol) of N-methylpiperazine was added and the mixture was stirred at 100° C. for 7 hours. Water was added to the reaction solution and the mixture was extracted twice with ethyl acetate. The organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:methanol=20:1) to give 350 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-7-(4-methylpiperazin-1-yl)-5-pivaloylamino-4H-1-benzopyran-4-one (yield: 58%).

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate
  2. washThe organic layer was washed once with water and once with an aqueous saturated solution of sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (chloroform:methanol=20:1)

Sources & evidence

ORD record
ord-6ece9d809a4e45e9bb063c8525ef690c
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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