Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-5-methyl-6-phenylpyridine-2-carboxamide 1-oxide

HRID 2095904Notes

Reaction equation

HRID 2095904 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]3[N:11]([CH:13]=[C:14]([NH:16][C:17]([CH:19]4[CH2:21][CH2:20]4)=[O:18])[N:15]=3)[CH:12]=2)=[C:4]([F:24])[CH:3]=1.[CH3:25][C:26]1[C:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[N+:30]([O-:38])[C:29]([C:39](O)=[O:40])=[CH:28][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH:19]1([C:17]([NH:16][C:14]2[N:15]=[C:10]3[CH:9]=[CH:8][C:7]([O:6][C:5]4[CH:22]=[CH:23][C:2]([NH:1][C:39]([C:29]5[N+:30]([O-:38])=[C:31]([C:32]6[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=6)[C:26]([CH3:25])=[CH:27][CH:28]=5)=[O:40])=[CH:3][C:4]=4[F:24])=[CH:12][N:11]3[CH:13]=2)=[O:18])[CH2:21][CH2:20]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581584865-Methyl-6-phenylpyridine-2-carboxylic acid 1-oxideHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158607N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-5-methyl-6-phenylpyridine-2-carboxamide 1-oxideYield 61.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (98.8 mg, 0.303 mmol) and 5-methyl-6-phenylpyridine-2-carboxylic acid 1-oxide (83.1 mg, 0.363 mmol) in N,N-dimethylformamide (1.0 mL) were added HATU (150 mg, 0.394 mmol) and N,N-diisopropylethylamine (104 μL, 0.606 mmol), and the mixture was stirred at room temperature for 3.5 hr. Ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture, and the mixture was extracted 3 times 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 obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate) to give a white solid. The obtained solid was washed with ethyl acetate to give the title compound (100 mg, 61%) as a white solid.

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe combined organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate)
  7. customto give a white solid
  8. washThe obtained solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-e0ae7a44461d41a9ab9c8930a1fe317f
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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