1,2-Dimethoxyethane → 4'-Hydroxy-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide

HRID 1378350Notes

Reaction equation

HRID 1378350 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]([C:21]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[O:22])[C:12]1[C:17]([O:18][CH3:19])=[N:16][C:15]([CH3:20])=[CH:14][N:13]=1)(=[O:10])=[O:9].[Si]([O:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)(C(C)(C)C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].C(COC)OC>O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[OH:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]([S:8]([N:11]([C:21]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[O:22])[C:12]3[C:17]([O:18][CH3:19])=[N:16][C:15]([CH3:20])=[CH:14][N:13]=3)(=[O:10])=[O:9])=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 111078154-(tert-Butyldimethylsilyloxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 18704832N-(isobutoxycarbonyl)-N-(3-methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide

Product 1

HCID 229112944'-Hydroxy-N-(isobutoxycarbonyl)-N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamideYield 45.5%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×

Procedure

A mixture of 2-iodo- N-(isobutoxycarbonyl)- N-(3-methoxy-5-methylpyrazin-2-yl) benzenesulphonamide (2.0 g), 4-(t-butyldimethylsilyloxy)benzeneboronic acid (1.0 g), prepared by the method described in GB 2276162, tetrakis(triphenylphosphine)palladium(O) (0.25 g), sodium carbonate (0.5 g), dimethoxyethane (10 ml) and water (10 ml) was stirred and heated under reflux for 18 hours. The mixture was allowed to cool and diluted with water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic extracts were washed with 0.1M sodium hydroxide solution (50 ml) and water (50 ml) and dried (MgSO4). The solvent was removed by evaporation and the residue purified by chromatography on a Mega Bond Elut column, eluting with 25% ethyl acetate in hexane. Fractions containing the required product were combined and evaporated to dryness to give 4'-hydroxy- N-(isobutoxycarbonyl)- N-(3-methoxy-5-methylpyrazin-2-yl)-2-biphenylsulphonamide as a solid (0.85g); 1H NMR (CDCl3): 0.7 (d, 6H), 1.59-1.79 (m, 1H), 2.49 (s, 3H), 3.83 (d, 2H), 3.96 (s, 3H), 5.15 (s, 1H), 6.78 (d, 2H), 7.24-7.38 (m, 3H), 7.50-7.59 (m, 2H), 7.91 (s, 1H), 8.57 (d, 1H); mass spectrum (+ve ESP): 472 (M+H)+.

Workup

  1. customprepared by the method
  2. temperatureheated
  3. temperatureunder reflux for 18 hours
  4. temperatureto cool
  5. extractionextracted with ethyl acetate (2×50 ml)
  6. washThe combined organic extracts were washed with 0.1M sodium hydroxide solution (50 ml) and water (50 ml)
  7. dry with materialdried (MgSO4)
  8. customThe solvent was removed by evaporation
  9. customthe residue purified by chromatography on a Mega Bond Elut column
  10. washeluting with 25% ethyl acetate in hexane
  11. additionFractions containing the required product
  12. customevaporated to dryness

Sources & evidence

ORD record
ord-450f1ef3f5e94233a2e63d81831b341d
Source dataset
uspto-grants-1997_09
Patent number
US05668137

Reaction notes

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