Sodium Carbonate → HCID 10026554, compound

HRID 497713Notes

Reaction equation

HRID 497713 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:17]1[CH:18]=[C:19]2[C:23](=[C:24]([F:27])[C:25]=1[F:26])[N:22]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[N:21]=[C:20]2[NH:36][C:37](=[O:41])[CH2:38][CH2:39][CH3:40]>O.O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:25]1[C:24]([F:27])=[C:23]2[C:19]([C:20]([NH:36][C:37](=[O:41])[CH2:38][CH2:39][CH3:40])=[N:21][N:22]2[CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])=[CH:18][C:17]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 10095181HCID 10095181, compound

Product 1

HCID 10026554HCID 10026554, compoundYield 96.3%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

469 mg of phenylboronic acid, 760 mg of sodium carbonate in 30 cm3 of water and 379 mg of tetrakis(triphenylphosphine)palladium are added to 1.15 g of N-(5-bromo-6,7-difluoro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl)butanamide, prepared in Example 104, in 150 cm3 of dioxane, and the mixture is refluxed for 4 hours. The reaction medium is diluted with 100 cm3 of ethyl acetate and 75 cm3 of water and filtered through a sinter funnel packed with Celite. The organic phase is separated out after settling of the phases has taken place, washed with 75 cm3 of water and with 75 cm3 of saturated sodium chloride solution, dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2 kPa; 50° C.) to give 2 g of crude product in the form of a black oil. The crude product is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume). The fractions containing the expected product are combined, evaporated under reduced pressure (2 kPa; 50° C.) and dried (90 Pa, 45° C.); to give 1.1 g of N-[6,7-difluoro-5-phenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

Workup

  1. temperaturethe mixture is refluxed for 4 hours
  2. filtrationfiltered through a sinter funnel
  3. customThe organic phase is separated out
  4. washwashed with 75 cm3 of water and with 75 cm3 of saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2 kPa; 50° C.)
  8. customto give 2 g of crude product in the form of a black oil
  9. customThe crude product is purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60 μm; diameter 3.5 cm), eluting with a cyclohexane/ethyl acetate mixture (85/15 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. customdried (90 Pa, 45° C.)

Sources & evidence

ORD record
ord-3ad38eb86e214ae09d8aed9c919bdeb4
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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