Cesium carbonate → N-{4-methyl-5-[2-(1-methyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-acetamide

HRID 2066782Notes

Reaction equation

HRID 2066782 reaction equation
[C:1]([NH:4][C:5]1[S:6][CH:7]=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]2([CH3:27])[CH2:26][CH2:25]2)[CH:19]=1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:10][C:8]1[N:9]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[S:6][C:7]=1[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]2([CH3:27])[CH2:26][CH2:25]2)[CH:19]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 280907N-(4-Methylthiazol-2-yl)acetamideHCID 574170884-Bromo-2-(1-methylcyclopropyl)pyridine

Product 1

HCID 86631917N-{4-methyl-5-[2-(1-methyl-cyclopropyl)-pyridin-4-yl]-thiazol-2-yl}-acetamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-acetamido-4-methylthiazole [7336-51-8] (60.4 mmol), cesium carbonate (110 mmol), tri-tert-butylphosphinium tetrafluoroborate (10.99 mmol), palladium (II) acetate (5.49 mmol) and 4-bromo-2-(1-methyl-cyclopropyl)-pyridine (Step 1.4) (54.9 mmol) in DMF (230 mL) was stirred for 3.5 h at 100° C. After cooling to rt, the reaction mixture was filtered and then concentrated. The residue was diluted with a saturated solution of NaHCO3 and extracted with EtOAc (3×). The combined organic phases were successively washed with a saturated solution of NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a pale yellow solid. HPLC: tR=4.37 min (method B); LC-MS: tR=1.47 min, [M+H]+ 288; TLC: Rf=0.26 (1:2 Hex/EtOAc).

Workup

  1. temperatureAfter cooling to rt
  2. filtrationthe reaction mixture was filtered
  3. concentrationconcentrated
  4. additionThe residue was diluted with a saturated solution of NaHCO3
  5. extractionextracted with EtOAc (3×)
  6. washThe combined organic phases were successively washed with a saturated solution of NaHCO3 and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified

Sources & evidence

ORD record
ord-a12752560bea411c866269eec1a16134
Source dataset
uspto-grants-2012_10
Patent number
US08293753B2

Reaction notes

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