Methyl iodide → Basimglurant

HRID 2067926Notes

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.[CH:23]([N-]C(C)C)(C)C.[Li+].IC>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[CH3:23])[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: -75 °C

Procedure

This compound was prepared according to the general procedure 3 described hereinabove. 2-chloro-4-[1-(4-fluoro-phenyl)-2-methyl-1H-imidazol-4-ylethynyl]-pyridine (200 mg, 0.607 mmol) was dissolved in 10 mL THF and cooled to −75° C. Lithiumdiisopropylamide (0.45 ml, 0.91 mmol) was added, and the mixture stirred for 15 min at −75° C. Iodomethane (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=326.5 (M+H+).

Workup

customThis compound was prepared
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-cced667fa4404edab14786f8a94e08ba
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293916B2

Reaction notes

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