Lithium Hexamethyldisilazide → 5-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide

HRID 1500710Notes

Reaction equation

CO[C:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:20]=[N:21][CH:22]=2)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[F:19])=[O:4].[CH:23]([O:25][CH2:26][CH2:27][O:28][NH2:29])=[CH2:24].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH:23]([O:25][CH2:26][CH2:27][O:28][NH:29][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[N:9]([CH:20]=[N:21][CH:22]=2)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[F:19])=[O:4])=[CH2:24]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-(2-fluoro-4-iodophenylamino)imidazo[1,5-a]pyridine-6-carboxylic acid methyl ester (1.5 g, 3.64 mmol) and O-(2-vinyloxyethyl)hydroxylamine (749 mg, 7.28 mmol) in THF (30 mL) at 0° C. was added lithium bis(trimethylsilyl)amide as a solution in THF (18 mL, 1M, 18 mmol) over 5 minutes. The reaction mixture was stirred at −0° C. for 1 hour before being quenched with saturated aqueous ammonium chloride. Volatile solvents were removed in vacuo and then diethyl ether (10 mL) and ethyl acetate (20 mL) added. The resultant mixture was sonicated causing a precipitate to form which was filtered off to give the title compound as a yellow solid (1.07 g, 61%). LCMS (Method B): RT=2.79 min, M+H+=483.

Workup

custombefore being quenched with saturated aqueous ammonium chloride
customVolatile solvents were removed in vacuo
additiondiethyl ether (10 mL) and ethyl acetate (20 mL) added
customThe resultant mixture was sonicated
customto form which
filtrationwas filtered off

Sources & evidence

ORD record: ord-6f644c10b25b4ba5801d31e098bdc669
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206174B2

Reaction notes

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