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

HRID 2191523Notes

Reaction equation

HRID 2191523 reaction equation
OC(CN1CCOCC1)CN1CCCC2NC(C=O)=C(C)C=2C1=O.[F:25][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].[F:59][C:60]1[C:65]([F:66])=[CH:64][CH:63]=[CH:62][C:61]=1C1C(F)=CC=C2C=1CC(=O)N2.N1CCCCC1>C(O)C>[F:59][C:60]1[C:65]([F:66])=[CH:64][CH:63]=[CH:62][C:61]=1[C:27]1[C:26]([F:25])=[CH:34][CH:33]=[C:32]2[C:28]=1/[C:29](=[CH:36]/[C:37]1[NH:46][C:45]3[CH2:44][CH2:43][CH2:42][N:41]([CH2:47][C@H:48]([OH:56])[CH2:49][N:50]4[CH2:51][CH2:52][O:53][CH2:54][CH2:55]4)[C:40](=[O:57])[C:39]=3[C:38]=1[CH3:58])/[C:30](=[O:35])[NH:31]2

Participants

5

Reactant 3

HCID 8082PiperidineHCID 592500644-(2,3-Difluoro-phenyl)-5-fluoro-1,3-dihydro-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 592500832-((Z)-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-((R)-2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneYield 78%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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 (84 mg, 0.25 mmol) and 4-(2,3-difluoro-phenyl)-5-fluoro-1,3-dihydro-indol-2-one 74 g (60 mg, 0.23 mmol) were dissolved in 2 ml of ethanol, and added with 35 μl of piperidine to the solution at room temperature. Upon completion of the addition, the mixture was heated to reflux for 2 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 (3 ml×2) and dried to obtain the title compound 2-((Z)-(4-(2,3-difluorophenyl)-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-((R)-2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 75 (100 mg, yield 78%) as an orange solid.

Workup

  1. additionUpon completion of the addition
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 2 hours
  4. filtrationfiltered
  5. washThe filter cake was washed with anhydrous ethanol (3 ml×2)
  6. customdried

Sources & evidence

ORD record
ord-ec3a2975add24540ab1039c5328afc5e
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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