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

HRID 2095942Notes

Reaction equation

HRID 2095942 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.[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:37]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:35]=[C:34]([C:42](O)=[O:43])[C:33]2=[O:45])=[CH:28][CH:27]=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(O)C.O1CCCC1.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:42]([C:34]5[C:33](=[O:45])[N:32]([C:29]6[CH:28]=[CH:27][C:26]([F:25])=[CH:31][CH:30]=6)[C:37]([C:38]([F:41])([F:39])[F:40])=[CH:36][CH:35]=5)=[O:43])=[CH:3][C:4]=4[F:24])=[CH:12][N:11]3[CH:13]=2)=[O:18])[CH2:21][CH2:20]1

Participants

10

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 581584761-(4-Fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylic acidHCID 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 58158464N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-1-(4-fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxamideYield 19.4%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide (90 mg, 0.276 mmol) and 1-(4-fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylic acid (100 mg, 0.331 mmol) in N,N-dimethylformamide (2 mL) were added N,N-diisopropylethylamine (95 μL, 0.552 mmol) and HATU (126 mg, 0.331 mmol), and the mixture was stirred at room temperature for 6 hr. Ethyl acetate, tetrahydrofuran 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 washed with ethyl acetate and collected by filtration. The obtained slightly yellow solid was suspended in ethanol (3 mL), and the mixture was stirred at 70° C. for 17 hr. The suspension was collected by filtration and washed with ethanol to give the title compound (32.7 mg, 19%) as a slightly yellow 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. washThe obtained residue was washed with ethyl acetate
  7. filtrationcollected by filtration
  8. customThe obtained slightly yellow solid
  9. stirringthe mixture was stirred at 70° C. for 17 hr
  10. filtrationThe suspension was collected by filtration
  11. washwashed with ethanol

Sources & evidence

ORD record
ord-26a15708b9f4489cb335e7afcaa1d6f1
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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