Lithium Hexamethyldisilazide → 5-(2-Fluoro-4-cyclopropylphenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester

HRID 2063985Notes

Reaction equation

[F:1][C:2]1[CH:8]=[C:7]([CH:9]2[CH2:11][CH2:10]2)[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:12][O:13][C:14]([C:16]1[CH:17]=[CH:18][C:19]2[N:20]([CH:23]=[N:24][CH:25]=2)[C:21]=1Cl)=[O:15].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH3:12][O:13][C:14]([C:16]1[CH:17]=[CH:18][C:19]2[N:20]([CH:23]=[N:24][CH:25]=2)[C:21]=1[NH:4][C:3]1[CH:5]=[CH:6][C:7]([CH:9]2[CH2:11][CH2:10]2)=[CH:8][C:2]=1[F:1])=[O:15]

Participants

Conditions

Temperature: -70 °C

Procedure

To a solution of 2-fluoro-4-cyclopropyl aniline (395 mg, 2.61 mmol) and 5-chloro-imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester (500 mg, 2.37 mmol) in THF under nitrogen at −70° C. (20 mL) was added lithium bis(trimethylsilyl) amide (4.98 mL, 1M solution, 4.98 mmol) dropwise. After stirring for 1 hour at −70° C. the reaction mixture was allowed to warm and then quenched with saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate (150 mL), the organic extract dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0-50% ethyl acetate in cyclohexane) to yield the title compound (573 mg, 60%). LCMS (Method B): RT=3.60 min, M+H+=326.

Workup

temperatureto warm
customquenched with saturated aqueous ammonium chloride
extractionThe mixture was extracted with ethyl acetate (150 mL)
extractionthe organic extract
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-184c020ef69847f09f91c6d30d2e66ed
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288408B2

Reaction notes

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