Sodium hydride → HCID 68814746, compound

HRID 732462Notes

Reaction equation

HRID 732462 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[H-].[Na+].CS(N)(=O)=O.[Na].[CH3:14][O:15][C:16](=[O:29])[C:17]1[CH:22]=[C:21]([N:23]([CH3:27])[CH2:24][CH2:25][CH3:26])[N:20]=[C:19](Cl)[CH:18]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C>C1COCC1.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:14][O:15][C:16](=[O:29])[C:17]1[CH:22]=[C:21]([N:23]([CH3:27])[CH2:24][CH2:25][CH3:26])[N:20]=[C:19]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:18]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86614997HCID 86614997, compoundHCID 866150102-Chloro-6-(methylpropylamino)-isonicotinic acid methyl ester

Product 1

HCID 68814746HCID 68814746, compoundYield 88.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve methane sulfonamide (951 mg, 10 mmol) in THF (30 mL). Add sodium hydride (380 mg, 9.5 mmol, 60% dispersion in mineral oil) and reflux for 3 h, cool to room temperature and concentrate. Charge a sealed flask with sodium methansulfonamide (478 mg, 4.09 mmol), 2-chloro-6-(methylpropylamino)-isonicotinic acid methyl ester (79 mg, 3.27 mmol), biphenyl-2-yl-di-tert-butylphosphane (98 mg, 0.33 mmol), and tris(dibenzylideneacetone)dipalladium (0) (150 mg, 0.16 mmol) in toluene (7 mL). Degas with argon, seal the vessel and heat at 100° C. for 16 h. Cool to room temperature, dilute with ethyl acetate, wash with water, aqueous sodium chloride, concentrate and purify (silica gel chromatography, eluting with 0:100 to 50:50 ethyl acetate:hexanes) to give the title compound as an oil (870 mg, 88%).

Workup

  1. concentrationconcentrate
  2. customDegas with argon
  3. customseal the vessel
  4. temperatureheat at 100° C. for 16 h
  5. temperatureCool to room temperature
  6. additiondilute with ethyl acetate
  7. washwash with water, aqueous sodium chloride
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 0:100 to 50:50 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-d7627c5ed363437fbacf43f35a9758dd
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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