Diisopropylethylamine → N-(4-((2-((cyclopropylcarbonyl)amino)imidazo(1,2-a)pyridin-6-yl)oxy)-3-fluorophenyl)-6-methyl-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide

HRID 2095903Notes

Reaction equation

HRID 2095903 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[N:31]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C: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[C:30](=[O:38])[N:31]([C:32]6[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=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 179666306-Methyl-2-oxo-1-phenyl-1,2-dihydro-pyridine-3-carboxylic acidHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 44595039N-(4-((2-((cyclopropylcarbonyl)amino)imidazo(1,2-a)pyridin-6-yl)oxy)-3-fluorophenyl)-6-methyl-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamideYield 57.1%

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 (70 mg, 0.215 mmol) and 6-methyl-2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxylic acid (59.1 mg, 0.258 mmol) in N,N-dimethylformamide (1.0 mL) were added HATU (98 mg, 0.258 mmol) and N,N-diisopropylethylamine (74 μL, 0.43 mmol), and the mixture was stirred at room temperature for 17 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 (ethyl acetate) to give a pale-yellow solid. The obtained pale-yellow solid was washed with ethyl acetate and collected by filtration to give the title compound (66 mg, 57%) 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 (ethyl acetate)
  7. customto give a pale-yellow solid
  8. washThe obtained pale-yellow solid was washed with ethyl acetate
  9. filtrationcollected by filtration

Sources & evidence

ORD record
ord-278f2d16b80c46a5b0050e2d4f0993ab
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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