Piperidine → 3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one

HRID 2191525Notes

Reaction equation

HRID 2191525 reaction equation
[OH:1][CH: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].FC1C=C2C(=CC=1)NC(=O)/C/2=C\[C:37]1[NH:46][C:45]2[CH2:44][CH2:43][CH2:42][N:41](C[C@H](O)CN3CCOCC3)[C:40](=[O:57])[C:39]=2[C:38]=1[CH3:58].[O:59]([C:61]1[CH:69]=[C:68]2[C:64]([CH2:65][C:66](=[O:70])[NH:67]2)=[CH:63][CH:62]=1)[CH3:60].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:65]3\[C:66](=[O:70])[NH:67][C:68]4[C:64]\3=[CH:63][CH:62]=[C:61]([O:59][CH3:60])[CH:69]=4)=[C:13]([CH3:14])[C:6]=2[C:5]1=[O:17].[CH3:58][C:38]1[C:39]2[C:40](=[O:57])[NH:41][CH2:42][CH2:43][CH2:44][C:45]=2[NH:46][CH:37]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 27937496-MethoxyoxindoleHCID 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 2

HCID 59250060(R,Z)-5-(2-hydroxy-3-morpholinopropyl)-2-((6-methoxy-2-oxoindolin-3-ylidene) methyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneHCID 867021093-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneYield 167.5%

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 6-methoxyl-1,3-dihydro-indol-2-one (13 mg, 0.08 mmol) were dissolved in 1560 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)-2-(6-methoxy-2-oxoindolin-3-ylidene) methyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 77 (22 mg, yield 51%) 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-ae7432dfbed24b6e8948542821335d5b
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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