Sodium Carbonate → N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamide

HRID 1585670Notes

Reaction equation

HRID 1585670 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]([C:18]1[O:22][N:21]=[C:20]([CH3:23])[C:19]=1[CH3:24])[CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])(=[O:10])=[O:9].B([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]([S:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)(=[O:39])=[O:38])[CH:29]=1)(O)O.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO>[CH3:23][C:20]1[C:19]([CH3:24])=[C:18]([N:11]([CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])[S:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[C:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[N:30]([S:37]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)(=[O:39])=[O:38])[CH:29]=2)(=[O:10])=[O:9])[O:22][N:21]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27762171-(phenylsulfonyl)-1H-indol-3-ylboronic acidHCID 106933732-bromo-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide

Product 1

HCID 21219232N-(3,4-Dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]-2-[1-(phenylsulfonyl)-1H-indol-3-yl]benzenesulfonamideYield 45%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
77.5 °C

Procedure

After purging a solution of 2-bromo-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide (595 mg; 1.42 mmol) in 14 ml of toluene and 12 ml of EtOH with argon for 20 minutes, the title product of Step (C) (600 mg; 1.99 mmol) was added followed by 2M Na2CO3 (10 ml; previously purged with argon) and tetrakis(triphenylphosphine)palladium(0) (200 mg). The heterogeneous mixture was heated to 75-80° C. for 5 hrs. After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (50 ml) and water (25 ml). The aqueous layer was extracted with an additional 25 ml of ethyl acetate and the combined organic layers were washed with water (25 ml) and brine (25 ml). After drying (MgSO4) and decolorizing (Darco), the green solution was concentrated to afford a dark green residue which was chromatographed on a 5×12 cm silica gel column, using 2 L EtOAc:hexanes, 1:3, 1 L EtOAc:hexanes, 3:7 and 1 L EtOAc:hexanes, 35:65 as the mobile phase. The pure fractions were concentrated to afford 379 mg (45%) of the title product of this step as a blue-green foam.

Workup

  1. custompreviously purged with argon) and tetrakis(triphenylphosphine)palladium(0) (200 mg)
  2. temperatureAfter cooling to room temperature
  3. customthe reaction mixture was partitioned between ethyl acetate (50 ml) and water (25 ml)
  4. extractionThe aqueous layer was extracted with an additional 25 ml of ethyl acetate
  5. washthe combined organic layers were washed with water (25 ml) and brine (25 ml)
  6. dry with materialAfter drying (MgSO4)
  7. concentrationthe green solution was concentrated
  8. customto afford a dark green residue which
  9. customwas chromatographed on a 5×12 cm silica gel column
  10. concentrationThe pure fractions were concentrated

Sources & evidence

ORD record
ord-1321334a58224526887dcd53a4e27305
Source dataset
uspto-grants-1999_08
Patent number
US05939446

Reaction notes

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