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

HRID 2191534Notes

Reaction equation

HRID 2191534 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].[Br:25][C:26]1[CH:27]=[C:28]([F:36])[CH:29]=[C:30]2[C:34]=1[NH:33][C:32](=[O:35])[CH2:31]2.N1CCCCC1>C(O)C>[Br:25][C:26]1[CH:27]=[C:28]([F:36])[CH:29]=[C:30]2[C:34]=1[NH:33][C:32](=[O:35])/[C:31]/2=[CH:15]\[C:12]1[NH:11][C:7]2[CH2:8][CH2:9][CH2:10][N:4]([CH2:3][C@@H:2]([OH:1])[CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[C:5](=[O:17])[C:6]=2[C:13]=1[CH3:14].[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][CH:12]=[C:13]([CH3:14])[C:6]=2[C:5]1=[O:17]

Participants

6

Reactant 3

HCID 8082PiperidineHCID 534188887-Bromo-5-fluoroindolin-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 2

HCID 25131960(S,Z)-2-((7-bromo-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneHCID 685234465-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-oneYield 260.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-5-(2-Hydroxy-3-morpholin-4-yl-propyl)-3-methyl-4-oxo-1,4,5,6,7,8-hexa hydro-pyrrolo[3,2-c]azepine-2-carbaldehyde 78f (40 mg, 0.12 mmol) and 7-bromo-5-fluoro-1,3-dihydro-indol-2-one 4b (27 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 reacted 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)-2-(7-bromo-5-fluoro-2-oxoindolin-3-ylidene)methyl)-5-(2-hydroxy-3-morpholinopropyl)-3-methyl-5,6,7,8-tetrahydropyrrolo[3,2-c]azepin-4(1H)-one 82 (48 mg, yield 73.8%) as a yellow solid.

Workup

  1. additionUpon completion of the addition
  2. customthe reaction mixture was reacted at 45° C. for 16 hours
  3. filtrationfiltered
  4. washThe filter cake was washed with anhydrous ethanol (1 ml×2)
  5. customdried

Sources & evidence

ORD record
ord-518580246529481694f7d4a0c4492737
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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