Citric Acid → N-[6-(4-aminophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

HRID 2095754Notes

Reaction equation

[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]4[CH:21]=[CH:20][C:19]([NH:22]C(=O)OCC5C=CC=CC=5)=[CH:18][CH:17]=4)=[CH:11][N:10]3[CH:33]=2)=[O:5])[CH2:3][CH2:2]1.[OH-].[Ba+2].[OH-].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(=O)([O-])O.[Na+]>COCCOC>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:12]2[CH:13]=[CH:14][C:9]3[N:10]([CH:33]=[C:7]([NH:6][C:4]([CH:1]4[CH2:2][CH2:3]4)=[O:5])[N:8]=3)[CH:11]=2)=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of benzyl [4-({2[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]carbamate (500 mg, 1.13 mmol) in 1,2-dimethoxyethane (15 mL) was added 0.15 mol/L aqueous barium hydroxide solution (10 mL), and the mixture was stirred at 90° C. for 36 hr. After cooling to room temperature, the reaction mixture was adjusted to pH about 5 with citric acid, and to pH about 10 with saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate/tetrahydrofuran, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100) to give the title compound (223 g, 64%).

Workup

temperatureAfter cooling to room temperature
extractionThe mixture was extracted with ethyl acetate/tetrahydrofuran
washthe organic layer was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
customThe solvent was evaporated under reduced pressure
customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)

Sources & evidence

ORD record: ord-c02f969c5d0740319a61bce48a2db43f
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445509B2

Reaction notes

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