Piperidine → (R,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 2191524Notes

Reaction equation

HRID 2191524 reaction equation
O[CH:2](CN1CCOCC1)CN1CCCC2NC(C=O)=C(C)C=2C1=O.F[C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:30](=[O:35])/[C:29]/2=[CH:36]\[C:37]1[NH:46][C:45]2[CH2:44][CH2:43][CH2:42][N:41]([CH2:47][C@H:48]([OH:56])[CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)[C:40](=[O:57])[C:39]=2[C:38]=1[CH3:58].CC1C=CC=C2C=1CC(=O)N2.N1CCCCC1>C(O)C>[OH:56][C@H:48]([CH2:49][N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1)[CH2:47][N:41]1[CH2:42][CH2:43][CH2:44][C:45]2[NH:46][C:37](/[CH:36]=[C:29]3\[C:30](=[O:35])[NH:31][C:32]4[C:28]\3=[C:27]([CH3:2])[CH:26]=[CH:34][CH:33]=4)=[C:38]([CH3:58])[C:39]=2[C:40]1=[O:57]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 125793824-Methyl-1,3-dihydro-2H-indol-2-oneHCID 86761721(R,Z)-2-(5-Fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-c]azepin-4-one 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 25131961(R,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 30%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

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 53f (30 mg, 0.09 mmol) and 4-methyl-1,3-dihydro-indol-2-one (12 mg, 0.08 mmol) were dissolved in 156 μl of ethanol, and added with 4.4 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 (R,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 76(12 mg, yield 30%) as a orange 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-730ccf3da3ac4bc6aeb45ae293e3e245
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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