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

HRID 1430147Notes

Reaction equation

HRID 1430147 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}-acetamideYield 83.9%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-acetamido-4-methylthiazole (405 mg, 2.6 mmol, 1.1 eq), cesium carbonate (1.54 g, 4.72 mmol, 2 eq), tri-tert-butylphosphinium tetrafluoroborate (137 mg, 0.47 mmol, 0.2 eq), palladium (II) acetate (51 mg, 0.24 mmol, 0.1 eq) and 4-bromo-2-(1-methyl-cyclopropyl)-pyridine (Step 40.4) (500 mg, 2.36 mmol) in DMF (10 mL) is stirred for 3.5 h at 100° C. under an argon atmosphere, allowed to cool, quenched by addition of a saturated solution of NaHCO3 and filtered through a pad of celite. The filtrate is extracted with EtOAc. The organic phase is washed with a saturated solution of NaHCO3, dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (DCM/MeOH, 1:0→99:1) to afford 569 mg of the title compound as a yellow solid: ESI-MS: 288.1 [M+H]+; TLC: Rf=0.40 (DCM/MeOH, 9:1).

Workup

  1. temperatureto cool
  2. customquenched by addition of a saturated solution of NaHCO3
  3. filtrationfiltered through a pad of celite
  4. extractionThe filtrate is extracted with EtOAc
  5. washThe organic phase is washed with a saturated solution of NaHCO3
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel column chromatography (DCM/MeOH, 1:0→99:1)

Sources & evidence

ORD record
ord-2541727431fb48cf856ff9f968e4888e
Source dataset
uspto-grants-2015_01
Patent number
US08940771B2

Reaction notes

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