Sodium Carbonate → 3-(2-Chloro-4-pyrimidinyl)-1-(phenylsulfonyl)-1H-indole

HRID 1947003Notes

Reaction equation

HRID 1947003 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20](B(O)O)=[CH:19]2)(=[O:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.O.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:9]1([S:15]([N:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)=[CH:19]2)(=[O:17])=[O:16])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 27762171-(phenylsulfonyl)-1H-indol-3-ylboronic acid

Product 1

HCID 597433323-(2-Chloro-4-pyrimidinyl)-1-(phenylsulfonyl)-1H-indole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 2,4-dichloropyrimidine (2.42 g, 16 mmol), 1-(phenylsulfonyl)-1H-indol-3-ylboronic acid (3.89 g, 13 mmol) and sodium carbonate (5.03 g, 47 mmol) in acetonitrile/water (2:1, 60 mL) was degassed with argon, then tetrakis(triphenylphosphine)palladium (300 mg, 1.6 mol) was added. The resulting mixture was heated to reflux for 2 h while a white suspension formed. The precipitate was cooled and filtered through a CELITE™/Silica gel plug. The filter cake was washed with EtOAc, the organic layer separated, washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was recrystallized from EtOAc/hexanes to give 1-benzenesulfonyl-3-(2-chloro-pyrimidin-4-yl)-1H-indole as a light-pink solid. The solid filtrate from the reaction mixture was dissolved in DCM, dried over Na2SO4, filtered, and combined with the previous batch of product. The collected solids were dissolved in DCM, the solvent was evaporated under reduced pressure and EtOAc was added to form a suspension, the product was filtered and washed with hexanes, to give 1-benzenesulfonyl-3-(2-chloro-pyrimidin-4-yl)-1H-indole (2.0 g, 33% yield) as a light-pink solid. An additional 0.45 g of product was obtained from the mother liquors.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 2 h while a white suspension
  3. customformed
  4. temperatureThe precipitate was cooled
  5. filtrationfiltered through a CELITE™/Silica gel plug
  6. washThe filter cake was washed with EtOAc
  7. customthe organic layer separated
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated under reduced pressure
  12. customThe residue was recrystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-4a798b99dadb4ab29c5b9362ff885879
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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