Lithium diisopropylamide → HCID 11175317, compound

HRID 491329Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:23])[N:13]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=3)[CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH:24]([N-]C(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:23])[N:13]([C:15]3[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=3)[C:14]=2[CH3:24])[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: -75 °C

Procedure

2-Chloro-4-[1-(3,5-difluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-pyridine (200 mg, 0.607 mmol) was dissolved in 10 mL THF and cooled to −75° C. Lithium diisopropylamide (0.45 ml, 0.91 mmol) was added and the mixture stirred for 15 min at −75° C. lodomethane (0.05 ml, 0.85 mmol) was added and stirring was continued at −75° C. for 2 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 90:10->20:80 gradient) and by recrystallization from ethyl acetate. The desired compound was obtained as a white solid (40 mg, 19%), MS: m/e=344.5 (M+H+).

Workup

additionwas added
stirringstirring
waitwas continued at −75° C. for 2 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 90:10->20:80 gradient) and by recrystallization from ethyl acetate

Sources & evidence

ORD record: ord-72bb83144985459a8262e412d5119202
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07531529B2

Reaction notes

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