Methanol → 5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid piperidin-4-ylamide

HRID 1664468Notes

Reaction equation

HRID 1664468 reaction equation
N1C2C(=NC=CC=2)N([N:10]2[C:14](/[CH:15]=[C:16]3\[C:17](=[O:26])[NH:18][C:19]4[C:24]\3=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[C:13]([CH3:27])[C:12]([C:28]([O-:30])=O)=[C:11]2[CH3:31])N=1.CO.[CH3:34][N:35]([CH:37]=O)C>[Pd]>[NH:35]1[CH2:37][CH2:31][CH:11]([NH:10][C:28]([C:12]2[C:13]([CH3:27])=[C:14](/[CH:15]=[C:16]3\[C:17](=[O:26])[NH:18][C:19]4[C:24]\3=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)[NH:10][C:11]=2[CH3:31])=[O:30])[CH2:12][CH2:34]1

Participants

5

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 131727992(Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 592159245-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid piperidin-4-ylamideYield 43.7%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

Steps 3 & 4: To the solution of (Z)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl 5-[(5-fluoro-2-oxoindolin-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxylate (A4) (0.2 g, 0.48 mmol) in 25 mL of DMF solution was added compound 6c (0.268 g, 0.58 mmol). The reaction mixture was stirred at room temperature for several hours. LC/MS detection was applied to determine completion of the reaction. 200 mg of 5% Pd/C was added to the mixture, followed by 25 mL of MeOH. The mixture was stirred under H2 atmosphere for 30 min and filtered. The filtrate was evaporated under reduced pressure and the residue was triturated with 5% diethylamine/methanol (25 mL) under sonication. The solid was collected by filtration and washed with methanol (5 mL*2), dried under vacuum to provide the title compound (80 mg, 43.7% yield) as orange solid. 1H NMR (300 MHz, DMSO-d6): δ=13.67 (s, 1H), 10.89 (s, 1H), 7.67-7.78 (m, 3H), 6.82-6.96 (m, 2H), 3.87-3.92 (m, 1H), 3.06-3.09 (d, 2H), 2.72-2.79 (t, 2H), 2.39-2.41 (ds, 6H), 1.84-1.89 (d, 6H), 1.46-1.57 (m, 2H). LC/MS: 383.1 [M+H]+.

Workup

  1. customcompletion of the reaction
  2. stirringThe mixture was stirred under H2 atmosphere for 30 min
  3. filtrationfiltered
  4. customThe filtrate was evaporated under reduced pressure
  5. customthe residue was triturated with 5% diethylamine/methanol (25 mL) under sonication
  6. filtrationThe solid was collected by filtration
  7. washwashed with methanol (5 mL*2)
  8. customdried under vacuum

Sources & evidence

ORD record
ord-2014e360fcd845c592ebf5e0d175f52b
Source dataset
uspto-grants-2011_10
Patent number
US08039470B2

Reaction notes

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