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

HRID 2095908Notes

Reaction equation

HRID 2095908 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]([C:32]2[C:33]([CH3:42])=[CH:34][CH:35]=[C:36]([C:39](O)=[O:40])[N+:37]=2[O-:38])=[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:36]5[N+:37]([O-:38])=[C:32]([C:29]6[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=6)[C:33]([CH3:42])=[CH:34][CH:35]=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 58158605N-[6-(4-amino-2-fluorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamideHCID 581586416-Carboxy-2-(4-fluorophenyl)-3-methylpyridin-1-ium-1-olate

Product 1

HCID 66968571N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxideYield 47.1%

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 (100 mg, 0.306 mmol) and 6-(4-fluorophenyl)-5-methylpyridine-2-carboxylic acid 1-oxide (98.9 mg, 0.367 mmol) in N,N-dimethylformamide (1.0 mL) were added HATU (140 mg, 0.368 mmol) and N,N-diisopropylethylamine (105 μL, 0.612 mmol), and the mixture was stirred at room temperature for 3 hr. Ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture, 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 obtained residue was purified by silica gel column chromatography (ethyl acetate) to give a white solid. The obtained white solid was washed with ethyl acetate to give the title compound (80 mg, 47%) as white crystals.

Workup

  1. extractionthe mixture was extracted twice 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 white solid
  8. washThe obtained white solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-7c69225db3b347ef99459299516cd047
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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