Sodium Carbonate → HCID 22319615, compound

HRID 497685Notes

Reaction equation

HRID 497685 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](=[CH:24][C:25]=1Br)[N:22]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:21]=[C:20]2[NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39]>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>[C:1]1([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][C:25]=2[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:22]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:21]=[C:20]3[NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 22319520HCID 22319520, compound

Product 1

HCID 22319615HCID 22319615, compoundYield 141.6%

Reagents, catalysts & solvents 4

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

Procedure

1.12 g of phenylboronic acid, 1.55 g of sodium carbonate in 40 cm3 of water and 463 mg of tetrakis(triphenylphosphine)palladium are added to 1 g of N-[5,6-dibromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described in Example 70, in 150 cm3 of dioxane, and the mixture is refluxed for 18 hours. The reaction medium is diluted with 100 cm3 of ethyl acetate and with 100 cm3 of water and is then filtered through a sinter funnel packed with Celite. The organic phase is separated out after settling of the phases has taken place and washed with 75 cm3 of saturated sodium chloride solution, separated out after settling of the phases has taken place, dried over magnesium sulphate, filtered and concentrated under reduced pressure (2 kPa; 50° C.) to give 2.6 g of crude product, which is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume). The fractions containing the expected product are combined, evaporated under reduced pressure (2 kPa; 50° C.) and then dried (90 Pa; 45° C.) to give 1.4 g of N-[5,6-diphenyl-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide in the form of a yellow oil.

Workup

  1. temperaturethe mixture is refluxed for 18 hours
  2. filtrationis then filtered through a sinter funnel
  3. customThe organic phase is separated out
  4. washwashed with 75 cm3 of saturated sodium chloride solution
  5. customseparated out
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure (2 kPa; 50° C.)
  9. customto give 2.6 g of crude product, which
  10. customis purified by chromatography under an argon pressure of 50 kPa
  11. washon a column of silica gel (particle size 40-60 μm; diameter 2.5 cm), eluting with a cyclohexane/ethyl acetate mixture (80/20 by volume)
  12. additionThe fractions containing the expected product
  13. customevaporated under reduced pressure (2 kPa; 50° C.)
  14. customdried (90 Pa; 45° C.)

Sources & evidence

ORD record
ord-411feb12f97c4ef4941b1ee443737354
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

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