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

HRID 2076166Notes

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-1deaaec4c4594e4e843efe85ca52b1fb
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07923456B2

Reaction notes

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