Water → HCID 19434807, compound

HRID 1736175Notes

Reaction equation

HRID 1736175 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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:55][Si:56]([C:59]#[CH:60])([CH3:58])[CH3:57].O>CN(C)C=O.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:27][C:26]1[C:2]([C:60]#[C:59][Si:56]([CH3:58])([CH3:57])[CH3:55])=[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]([CH3:21])([CH3:20])[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

8

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 10578638HCID 10578638, compound

Product 1

HCID 19434807HCID 19434807, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

30 mg (0.054mmol) 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 a mixed solvent of 0.5 mL of dimethylformamide and 0.5 mL of triethylamine, 1 mg (0.004 mmol) of palladium (II) acetate, 2 mg (0.008 mmol) of triphenylphosphine and 38 μL (0.27 mmol) of trimethylsilylacetylene were added and the mixture was stirred at 50° C. for 2 hours. The reaction solution was cooled to room temperature, water was added thereto and the mixture was extracted once with ethyl acetate. The organic layer was washed twice with 2N hydrochloric acid, 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 preparative thin layer chromatography (chloroform:acetonitrile=19:1) to give 12 mg of 6,8-difluoro-2-(3-fluoro-4-pivaloylaminophenyl)-5-pivaloylamino-7-(2-trimethylsilylethynyl)-4H-1-benzopyran-4-one (yield: 39%).

Workup

  1. additionwere added
  2. temperatureThe reaction solution was cooled to room temperature
  3. extractionthe mixture was extracted once with ethyl acetate
  4. washThe organic layer was washed twice with 2N hydrochloric acid, once with water and once with an aqueous saturated solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography (chloroform:acetonitrile=19:1)

Sources & evidence

ORD record
ord-a0db5eacc3924ce59bf402124a2e642b
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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