Cesium carbonate → N-[4-Methyl-5-(5-phenylsulfonylpyridin-3-yl)-1,3-thiazol-2-yl]acetamide

HRID 252728Notes

Reaction equation

HRID 252728 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[S:12][C:11]([NH:13][C:14](=[O:16])[CH3:15])=[N:10][C:9]=2[CH3:17])[CH:5]=[N:6][CH:7]=1.[C:18]1([S:24]([O-:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Na+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1>[CH3:17][C:9]1[N:10]=[C:11]([NH:13][C:14](=[O:16])[CH3:15])[S:12][C:8]=1[C:4]1[CH:5]=[N:6][CH:7]=[C:2]([S:24]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:26])=[O:25])[CH:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2723840Benzenesulfinic acid, sodium saltHCID 86244439HCID 86244439, compound

Product 1

HCID 86244440N-[4-Methyl-5-(5-phenylsulfonylpyridin-3-yl)-1,3-thiazol-2-yl]acetamideYield 22.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of N-[5-(5-bromopyridin-3-yl)-4-methyl-1,3-thiazol-2-yl]acetamide (26 mg), sodium benzenesulfinate (17 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (2.9 mg), caesium carbonate (41 mg) and toluene (3 mL) was purged with nitrogen. Tris(dibenzylideneacetone)dipalladium(0) (1.9 mg) was added and the reaction mixture was heated to 110° C. for 16 hours under a nitrogen atmosphere. A further portion of sodium benzenesulfinate (14 mg) and DMF (1 mL) were added and the reaction mixture was transferred to a microwave vial and heated in a microwave apparatus to 145° C. for 4 hours. The resultant mixture was evaporated and the residue was partitioned between dichloromethane and water. The organic phase was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by ‘basic reversed-phase chromatography’ as described hereinbefore. There was thus obtained the title compound as a solid (7 mg); 1H NMR Spectrum: (DMSOd6) 2.24 (s, 3H), 2.42 (s, 3H), 7.72 (m, 2H), 7.81 (m, 1H), 8.17 (m, 2H), 8.37 (m, 1H), 9.01 (m, 1H), 9.12 (m, 1H), 12.32 (s, 1H); Mass Spectrum: M+H+ 374.

Workup

  1. customwas purged with nitrogen
  2. additionTris(dibenzylideneacetone)dipalladium(0) (1.9 mg) was added
  3. additionA further portion of sodium benzenesulfinate (14 mg) and DMF (1 mL) were added
  4. temperatureheated in a microwave apparatus to 145° C. for 4 hours
  5. customThe resultant mixture was evaporated
  6. customthe residue was partitioned between dichloromethane and water
  7. washThe organic phase was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. customThe residue was purified by ‘basic reversed-phase chromatography’

Sources & evidence

ORD record
ord-c8b21cc1b7d6439ebc9e90d7afb06a60
Source dataset
uspto-grants-2011_01
Patent number
US07868188B2

Reaction notes

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