Cesium carbonate → N-[5-(2-tert-butyl-pyridin-4-yl)-4-methyl-thiazol-2-yl]acetamide

HRID 2370362Notes

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2-acetamido-4-methylthiazole (1.2 g, 7.7 mmol, 1.1 eq), cesium carbonate (4.55 g, 14 mmol, 2 eq), tri-tert-butylphosphinium tetrafluoroborate (0.406 g, 1.4 mmol, 0.2 eq), palladium (II) acetate (0.15 g, 0.7 mmol, 0.1 eq) and 4-bromo-2-tert-butyl-pyridine (Step 1.4) (1.5 g, 7 mmol) in DMF (50 mL) is stirred for 1.5 h at 90° 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→97:3) to afford 2.02 g of the title compound as a yellow solid: ESI-MS: 290.1 [M+H]+; TLC: Rf=0.35 (DCM/MeOH, 9:1).

Workup

temperatureto cool
customquenched by addition of a saturated solution of NaHCO3
filtrationfiltered through a pad of celite
extractionThe filtrate is extracted with EtOAc
washThe organic phase is washed with a saturated solution of NaHCO3
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue is purified by silica gel column chromatography (DCM/MeOH, 1:0→97:3)

Sources & evidence

ORD record: ord-738eb670152a4b0aacbf0fb3b96ff88d
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710085B2

Reaction notes

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