Thiophene → (+/-)-cis-4-[4-(5,6-dihydro-11H-imidazo [2,1-b][3]benzazepin-11-ylidene)-1-piperidinyl]-1-(3,5-dimethylbenzoyl)-2-(phenylmethyl)piperidine

HRID 1068660Notes

Reaction equation

HRID 1068660 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([CH3:24])[CH:23]=1)[C:5]([N:7]1[CH2:12][CH2:11][C:10](=O)[CH2:9][CH:8]1[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6].[NH:25]1[CH2:30][CH2:29][C:28](=[C:31]2[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[CH2:35][CH2:34][N:33]3[CH:42]=[CH:43][N:44]=[C:32]23)[CH2:27][CH2:26]1.S1C=CC=C1>CO.[Pd]>[N:44]1[CH:43]=[CH:42][N:33]2[CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[C:31](=[C:28]3[CH2:27][CH2:26][N:25]([C@H:10]4[CH2:11][CH2:12][N:7]([C:5](=[O:6])[C:4]5[CH:3]=[C:2]([CH3:1])[CH:23]=[C:22]([CH3:24])[CH:21]=5)[C@@H:8]([CH2:14][C:15]5[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=5)[CH2:9]4)[CH2:30][CH2:29]3)[C:32]=12

Participants

6

Reactant 3

HCID 8030ThiopheneHCID 186124926,11-dihydro-11-(4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepineHCID 18630826(+/-)-1-(3,5-Dimethylbenzoyl)-2-(phenylmethyl)-4-piperidinone

Product 1

HCID 86757037(+/-)-cis-4-[4-(5,6-dihydro-11H-imidazo [2,1-b][3]benzazepin-11-ylidene)-1-piperidinyl]-1-(3,5-dimethylbenzoyl)-2-(phenylmethyl)piperidineYield 12.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of (±)-1-(3,5-dimethylbenzoyl)-2-(phenylmethyl)-4-piperidinone (2.5 g) and 6,11-dihydro-11-(4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine (2.1 g) in methanol (150 ml) and a solution of thiophene (4%; 1 ml) was hydrogenated at 50° C. overnight with palladium on activated carbon (10%; 2 g) as a catalyst. After uptake of hydrogen, the catalyst was filtered off and the filtrate was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/ (CH3OH/ NH3) 98/2 to 95/5). The desired fraction was collected, the solvent evaporated, yielding 0.54 g (12.3%) of (±)-cis-4-[4-(5,6-dihydro-11H-imidazo [2,1-b][3]benzazepin-11-ylidene)-1-piperidinyl]-1-(3,5-dimethylbenzoyl)-2-(phenylmethyl)piperidine (comp. 1; mp. 138.7° C.).

Workup

  1. filtrationAfter uptake of hydrogen, the catalyst was filtered off
  2. customthe filtrate was evaporated
  3. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/ (CH3OH/ NH3) 98/2 to 95/5)
  4. customThe desired fraction was collected
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-8ab199b509d146a889e6c8719341babf
Source dataset
uspto-grants-2001_06
Patent number
US06251894B1

Reaction notes

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