Piperidine → (S,Z)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-2-((4-methyl-2-oxoindolin-3-ylidene)methyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one

HRID 2191535Notes

Reaction equation

HRID 2191535 reaction equation
[OH:1][C@@H:2]([CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[CH2:3][N:4]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:11][C:12]([CH:15]=O)=[C:13]([CH3:14])[C:6]=2[C:5]1=[O:17].[CH3:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:27]=1[CH2:28][C:29](=[O:35])[NH:30]2.N1CCCCC1>C(O)C>[OH:1][C@@H:2]([CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[CH2:3][N:4]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:11][C:12](/[CH:15]=[C:28]3\[C:29](=[O:35])[NH:30][C:31]4[C:27]\3=[C:26]([CH3:25])[CH:34]=[CH:33][CH:32]=4)=[C:13]([CH3:14])[C:6]=2[C:5]1=[O:17]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 125793824-Methyl-1,3-dihydro-2H-indol-2-oneHCID 59250080(S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde

Product 1

HCID 25131610(S,Z)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-2-((4-methyl-2-oxoindolin-3-ylidene)methyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneYield 63.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

(S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 78f (40 mg, 0.12 mmol 1) and 4-methyl-1,3-dihydro-indol-2-one (18 mg, 0.12 mmol) were dissolved in 1.5 ml of ethanol, and added with 6 μl of piperidine to the solution at room temperature. Upon completion of the addition, the reaction mixture was stirred at 45° C. for 16 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled to room temperature, and filtered. The filter cake was washed with anhydrous ethanol (1 ml×2) and dried to obtain the title compound (S,Z)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-2-((4-methyl-2-oxoindolin-3-ylidene)methyl)-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 83 (35 mg, yield 63.6%) as a yellow solid.

Workup

  1. additionUpon completion of the addition
  2. temperaturethe reaction mixture was naturally cooled to room temperature
  3. filtrationfiltered
  4. washThe filter cake was washed with anhydrous ethanol (1 ml×2)
  5. customdried

Sources & evidence

ORD record
ord-54fae3a40fee432ea9bc6f5882125156
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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