1,4'-Bipiperidine → HCID 86751342, compound

HRID 1379219Notes

Reaction equation

HRID 1379219 reaction equation
[F:1][C:2]([F:38])([F:37])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)[CH2:10][C@H:9]1[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)=[O:7].[N:39]1([CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl>[F:37][C:2]([F:1])([F:38])[C:3]1[CH:4]=[C:5]([CH:30]=[C:31]([C:33]([F:35])([F:34])[F:36])[CH:32]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][C:17]([N:48]2[CH2:49][CH2:50][CH:45]([N:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[CH2:46][CH2:47]2)=[O:19])[CH2:10][C@H:9]1[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)=[O:7]

Participants

6

Reactant 4

HCID 786071,4'-BipiperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86751304HCID 86751304, compound

Product 1

HCID 86751342HCID 86751342, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-(3-carboxypropyl)-2-(1H-indol-3-yl-methyl)piperazine (180 mg), 4-piperidinopiperidine (56 mg) and 1-hydroxybenzotriazole hydrate (45 mg) in dichloromethane (4 ml) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (64 mg) at ice-bath temperature. After stirring for 30 minutes, the reaction mixture was allowed to warm to room temperature and was stirred for 2 hours and 40 minutes. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water. The organic layer was washed successively with aqueous saturated sodium bicarbonate and brine, and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and methanol (10:1) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[3-(4,1'-bipiperidin-1-yl-carbonyl)propyl]-2-(1H-indol-3-yl-methyl)piperazine, which was converted to the corresponding dihydrochloride salt (0.18 g) by treatment with 4N hydrogen chloride in dioxane solution.

Workup

  1. stirringwas stirred for 2 hours and 40 minutes
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. customthe resulting residue was partitioned between ethyl acetate and water
  4. washThe organic layer was washed successively with aqueous saturated sodium bicarbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter evaporation of the solvent
  7. customthe residue was purified by column chromatography on silica gel eluting with a mixture of dichloromethane and methanol (10:1)

Sources & evidence

ORD record
ord-2770750347f24e8ab448b89ba0564165
Source dataset
uspto-grants-1997_09
Patent number
US05670505

Reaction notes

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