Diisopropylethylamine → N-[4-({2-[(cyclopropylcarbonyl)amino]-3-methylimidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 2095932Notes

Reaction equation

HRID 2095932 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]([C:15]([OH:17])=O)[C:9]2=[O:18])=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:42]=[CH:41][C:23]([O:24][C:25]2[CH:26]=[CH:27][C:28]3[N:29]([C:31]([CH3:40])=[C:32]([NH:34][C:35]([CH:37]4[CH2:39][CH2:38]4)=[O:36])[N:33]=3)[CH:30]=2)=[C:22]([F:43])[CH:21]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])O.[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH:37]1([C:35]([NH:34][C:32]2[N:33]=[C:28]3[CH:27]=[CH:26][C:25]([O:24][C:23]4[CH:41]=[CH:42][C:20]([NH:19][C:15]([C:10]5[C:9](=[O:18])[N:8]([C:5]6[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=6)[C:13]([CH3:14])=[CH:12][CH:11]=5)=[O:17])=[CH:21][C:22]=4[F:43])=[CH:30][N:29]3[C:31]=2[CH3:40])=[O:36])[CH2:38][CH2:39]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 210815291-(4-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acidHCID 58158557N-[6-(4-amino-2-fluorophenoxy)-3-methylimidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158545N-[4-({2-[(cyclopropylcarbonyl)amino]-3-methylimidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamideYield 75.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid (56.7 mg, 0.229 mmol) and N-[6-(4-amino-2-fluorophenoxy)-3-methylimidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (60 mg, 0.176 mmol) in N,N-dimethylformamide (1 mL) were added N,N-diisopropylethylamine (61 μL, 0.352 mmol) and HATU (87 mg, 0.229 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 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 alone) to give a yellow oil. The obtained oil was dissolved in ethyl acetate (1 mL) and left standing at room temperature for 17 hr. The precipitated solid was collected by filtration, washed with diethyl ether and collected by filtration to give the title compound (76 mg, 75%) as a white solid.

Workup

  1. extractionthe mixture was extracted 3 times with ethyl acetate
  2. washThe 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 alone)
  7. customto give a yellow oil
  8. waitleft
  9. waitstanding at room temperature for 17 hr
  10. filtrationThe precipitated solid was collected by filtration
  11. washwashed with diethyl ether
  12. filtrationcollected by filtration

Sources & evidence

ORD record
ord-fdf24cd5ccdb4c26a4588c733b684a13
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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