Hydrochloric Acid → N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxide hydrochloride

HRID 2095909Notes

Reaction equation

HRID 2095909 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:23]([C:25]5[N+:26]([O-:39])=[C:27]([C:32]6[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=6)[C:28]([CH3:31])=[CH:29][CH:30]=5)=[O:24])=[CH:18][C:17]=4[F:40])=[CH:11][N:10]3[CH:41]=2)=[O:5])[CH2:3][CH2:2]1.[ClH:42]>C(O)C.C(OCC)(=O)C.C(C(C)=O)C>[ClH:42].[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:23]([C:25]5[N+:26]([O-:39])=[C:27]([C:32]6[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=6)[C:28]([CH3:31])=[CH:29][CH:30]=5)=[O:24])=[CH:18][C:17]=4[F:40])=[CH:11][N:10]3[CH:41]=2)=[O:5])[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 66968571N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxide

Product 1

HCID 66968812N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxide hydrochlorideYield 46%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxide (1.54 g, 2.77 mmol) in ethanol (15 mL) was added and dissolved therein 6N hydrochloric acid (554 μL, 3.32 mmol), and the mixture was left standing at room temperature overnight. The precipitate was collected by filtration and washed with ethanol to give a white powder. The white powder was dissolved in ethyl acetate, tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethanol (30 mL) and heated to 80° C. 6N Hydrochloric acid (370 μL, 2.22 mmol) was added dropwise and dissolved therein. The solution was allowed to gradually cool to 50° C., and the mixture was stirred for 6 hr. The precipitate was collected by filtration and washed with ethanol to give a white solid. The white solid was suspended in methyl ethyl ketone (10 mL), and the suspension was stirred at 50° C. overnight. The precipitate was collected by filtration and washed with methyl ethyl ketone to give the title compound (747 mg, 46%) as white crystals.

Workup

  1. additionwas added
  2. dissolutiondissolved
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with ethanol
  5. customto give a white powder
  6. extractiontetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted twice with ethyl acetate
  7. washThe combined organic layer was washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent was evaporated under reduced pressure
  11. dissolutiondissolved
  12. temperatureto gradually cool to 50° C.
  13. filtrationThe precipitate was collected by filtration
  14. washwashed with ethanol
  15. customto give a white solid
  16. stirringthe suspension was stirred at 50° C. overnight
  17. filtrationThe precipitate was collected by filtration
  18. washwashed with methyl ethyl ketone

Sources & evidence

ORD record
ord-23572836e52940f1838ab4906376e429
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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