Piperidine → (S,Z)-2-(7-bromo-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one

HRID 2068740Notes

Reaction equation

HRID 2068740 reaction equation
[OH:1][C@@H:2]([CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[CH2:3][N:4]1[CH2:9][CH2:8][C:7]2[NH:10][C:11]([CH:14]=O)=[C:12]([CH3:13])[C:6]=2[C:5]1=[O:16].[Br:24][C:25]1[CH:26]=[C:27]([F:35])[CH:28]=[C:29]2[C:33]=1[NH:32][C:31](=[O:34])[CH2:30]2.N1CCCCC1>C(O)C>[Br:24][C:25]1[CH:26]=[C:27]([F:35])[CH:28]=[C:29]2[C:33]=1[NH:32][C:31](=[O:34])/[C:30]/2=[CH:14]\[C:11]1[NH:10][C:7]2[CH2:8][CH2:9][N:4]([CH2:3][C@@H:2]([OH:1])[CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:5](=[O:16])[C:6]=2[C:12]=1[CH3:13]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 534188887-Bromo-5-fluoroindolin-2-oneHCID 59375986(S)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde

Product 1

HCID 25207651(S,Z)-2-(7-bromo-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-oneYield 75.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde 5f (40 mg, 0.125 mmol) was dissolved in 2 mL of ethanol under stirring at room temperature, and 7-bromo-5-fluoro-1,3-dihydro-indol-2-one 12b (25.8 mg, 0.112 mmol) was then added to the solution. Upon completion of the addition, the reaction mixture was stirred until all dissolved, and piperidine (0.05 mL, 0.5 mmol) was then added to the solution. Upon completion of the addition, the reaction mixture was heated to reflux in an oil bath for 2 hours. The reaction was completed until TLC showed the disappearance of starting materials, and the reaction mixture was naturally cooled down to room temperature, and filtered under reduced pressure to give the title compound (S,Z)-2-(7-bromo-5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 12 (45 mg, 75.4%) as a yellow solid.

Workup

  1. additionUpon completion of the addition
  2. additionwas then added to the solution
  3. additionUpon completion of the addition
  4. temperaturethe reaction mixture was heated
  5. temperatureto reflux in an oil bath for 2 hours
  6. temperaturethe reaction mixture was naturally cooled down to room temperature
  7. filtrationfiltered under reduced pressure

Sources & evidence

ORD record
ord-2e8bf7156b684a819cb26623060b9119
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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