Sodium Carbonate → HCID 22319506, compound

HRID 497670Notes

Reaction equation

HRID 497670 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][C:26]=1[Cl:27])[N:23]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[N:22]=[C:21]2[NH:36][C:37](=[O:41])[CH2:38][CH2:39][CH3:40]>O.O1CCOCC1.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:1][C:2]1[CH:7]=[CH:6][C:5]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][C:26]=2[Cl:27])[N:23]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:35])[CH3:33])[N:22]=[C:21]3[NH:36][C:37](=[O:41])[CH2:38][CH2:39][CH3:40])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 22319528N-[5-bromo-6-chloro-1-[(2-trimethylsilylethoxy)methyl]indazol-3-yl]butanamide

Product 1

HCID 22319506HCID 22319506, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

470 mg of 4-fluorophenylboronic acid, 593 mg of sodium carbonate in 40 cm3 of water and 155 mg of tetrakis(triphenylphosphine)palladium are added to 1 g of N-[5-bromo-6-chloro-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide, described in Example 58, in 40 cm3 of dioxane. The mixture is refluxed for 18 hours and the reaction medium is filtered through a sinter funnel packed with Celite. 60 cm3 of ethyl acetate and 50 cm3 of distilled water are added to the filtrate. The organic phase is washed with 2×20 cm3 of saturated aqueous sodium chloride solution and then separated out after settling of the phases has taken place and dried over magnesium sulphate. After filtration, the filtrate is concentrated to dryness under reduced pressure (2 kPa; 50° C.) and the residue is purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume). The fractions containing the expected product are combined and evaporated under reduced pressure (2 kPa; 50° C.). After drying (90 Pa; 45° C.), 0.75 g of N-[5-(4-fluorophenyl)-6-chloro-1-[(2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide is thus obtained in the form of a yellow wax.

Workup

  1. temperatureThe mixture is refluxed for 18 hours
  2. filtrationthe reaction medium is filtered through a sinter funnel
  3. addition60 cm3 of ethyl acetate and 50 cm3 of distilled water are added to the filtrate
  4. washThe organic phase is washed with 2×20 cm3 of saturated aqueous sodium chloride solution
  5. customseparated out
  6. dry with materialdried over magnesium sulphate
  7. filtrationAfter filtration
  8. concentrationthe filtrate is concentrated to dryness under reduced pressure (2 kPa; 50° C.)
  9. customthe residue is purified by chromatography under an argon pressure of 50 kPa
  10. washon a column of silica gel (particle size 40-60 μm; diameter 4.5 cm), eluting with a cyclohexane/ethyl acetate mixture (90/10 by volume)
  11. additionThe fractions containing the expected product
  12. customevaporated under reduced pressure (2 kPa; 50° C.)
  13. dry with materialAfter drying (90 Pa; 45° C.), 0.75 g of N-[5-(4-fluorophenyl)-6-chloro-1-[(2-(trimethylsilyl)ethoxy]methyl]-1H-indazol-3-yl]butanamide
  14. customis thus obtained in the form of a yellow wax

Sources & evidence

ORD record
ord-6429f41984634bf8ad0270a5175c6dee
Source dataset
uspto-grants-2005_09
Patent number
US06949579B2

Reaction notes

Loading…