Dimethylformamide → 5-(2-Chloro-pyridin-4-ylethynyl)-3-(4-fluoro-phenyl)-2-methyl-3H-imidazole-4-carbaldehyde

HRID 2067942Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:22])[N:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([N-]C(C)C)(C)C.[Li+].CN(C)[CH:33]=[O:34]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:22])[N:13]([C:15]3[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=3)[C:14]=2[CH:33]=[O:34])[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: -70 °C

Procedure

2-chloro-4-[1-(4-fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-pyridine (2.0 g, 6.42 mmol) was dissolved in 50 mL THF and cooled to −70° C. Lithiumdiisopropylamide 2M/THF (4.8 ml, 9.6 mmol) was added, and the mixture stirred for 15 min at −70° C. Dimethylformamide (0.69 ml, 9.0 mmol) was added and stirring was continued at −70° C. for 3 hrs. The reaction mixture was quenched with sat. NaHCO3− solution and extracted with water and ethyl acetate. The combined organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (heptane/ethylacetate 1:2). The desired compound was obtained as a yellow solid (220 mg, 10%), MS: m/e=340.0 (M+H+).

Workup

stirringstirring
waitwas continued at −70° C. for 3 hrs
customThe reaction mixture was quenched with sat. NaHCO3− solution
extractionextracted with water and ethyl acetate
dry with materialThe combined organic extracts were dried with sodium sulfate
filtrationfiltered
customevaporated
customThe crude product was purified by flash chromatography on silica gel (heptane/ethylacetate 1:2)

Sources & evidence

ORD record: ord-d9b622b46ade4c00a9165e4293d5d05e
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293916B2

Reaction notes

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