Cesium carbonate → Ethyl 8-[(3,5-difluoropyridine-4-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate

HRID 1844192Notes

Reaction equation

[OH:1][C:2]1[C:3]2[N:4]([C:9]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:10]([CH3:12])[N:11]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[CH2:19][C:20]1[C:25]([F:26])=[CH:24][N:23]=[CH:22][C:21]=1[F:27].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:27][C:21]1[CH:22]=[N:23][CH:24]=[C:25]([F:26])[C:20]=1[CH2:19][O:1][C:2]1[C:3]2[N:4]([C:9]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:10]([CH3:12])[N:11]=2)[CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

5.0 g (21.34 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate from Example 87A and 3.83 g (23.48 mmol) of 4-(chloromethyl)-3,5-difluoropyridine from Example 115A were initially charged in 306 ml of abs. DMF, and 20.8 g (64.03 mmol) of caesium carbonate were added. The reaction mixture was stirred at 60° C. overnight. The reaction mixture, cooled to RT, was filtered, washed with ethyl acetate and concentrated. The residue was purified by silica gel chromatography (cyclohexane/ethyl acetate gradient=4:1 to 2:1). This gave 5.40 g (70% of theory) of the target compound.

Workup

temperatureThe reaction mixture, cooled to RT
filtrationwas filtered
washwashed with ethyl acetate
concentrationconcentrated
customThe residue was purified by silica gel chromatography (cyclohexane/ethyl acetate gradient=4:1 to 2:1)

Sources & evidence

ORD record: ord-10789e9e581a42f49dda858e6a82620f
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08946215B2

Reaction notes

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