Sodium Iodide → 8-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

HRID 2067018Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18](Br)=[CH:17][C:16]=1[F:22])=[O:4].[I-:23].[Na+].CN[C@@H]1CCCC[C@H]1NC.C(OCC)(=O)C>O1CCOCC1.CO.ClCCl.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([I:23])=[CH:17][C:16]=1[F:22])=[O:4]

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 8-(4-bromo-2-fluoro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (235 mg, 0.65 mmol), copper (I) iodide (6 mg, 0.03 mmol), sodium iodide (195 mg, 1.3 mmol) and trans-N,N′-dimethyl-1,2-cyclohexane diamine (0.01 mL, 0.06 mmol) in 1,4-dioxane (1.0 mL) was heated at 110° C. for 26 hours under an argon atmosphere. The reaction mixture was cooled to room temperature, diluted with methanol and loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was then washed with methanol and the desired product was subsequently eluted using 2M NH3 in MeOH. The eluent was collected and concentrated to give a residue. The residue was subjected to flash chromatography (Si-PPC, gradient 0% to 20%, ethyl acetate in dichloromethane) to afford the title compound as a pale yellow solid (182 mg, 67%). LCMS (method B): RT=3.45 min, [M+H]+=412.

Workup

temperatureThe reaction mixture was cooled to room temperature
washThe cartridge was then washed with methanol
washthe desired product was subsequently eluted
customThe eluent was collected
concentrationconcentrated
customto give a residue

Sources & evidence

ORD record: ord-e994eb7e2135414989f9b2c1ef54d141
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293763B2

Reaction notes

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