Piperidine → Henatinib

HRID 2191489Notes

Reaction equation

HRID 2191489 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].FC1C=C2C(=CC=1)NC(=O)C2.N1CCCCC1>C(O)C>[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[CH2:51][CH2:52][O:53][CH2:54][CH2:55]3)[C:40](=[O:57])[C:39]=2[C:38]=1[CH3:58]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 37310125-fluoro-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 25116064HenatinibYield 57,298.699%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(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 53f (50 mg, 0.149 mmol) was dissolved in 261 μl of ethanol under stirring, and added with 5-fluoro-1,3-dihydro-indol-2-one (20.28 mg, 0.134 mmol) and piperidine (7.3 μl, 0.074 mmol) to the solution at room temperature. Upon completion of the addition, the reaction mixture was stirred for 2 hours in dark at 80° C. in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed, and the reaction mixture was naturally cooled down to room temperature, filtered and dried to obtain the title compound (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 53 (40 g, yield 57%) as a yellow solid.

Workup

  1. additionUpon completion of the addition
  2. stirringthe reaction mixture was stirred for 2 hours in dark at 80° C. in an oil bath
  3. customthe oil bath was removed
  4. filtrationfiltered
  5. customdried

Sources & evidence

ORD record
ord-c0be775525b741d482da97ac1acc18f2
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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