Sodium Hydroxide → HCID 178468420, compound

HRID 1855666Notes

Reaction equation

HRID 1855666 reaction equation
[NH2:1][C@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:3]([N:5]1[CH2:10][CH2:9][C:8]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6]1)=[O:4].Cl[C:32](OC1C=CC([N+]([O-])=O)=CC=1)=[O:33].[NH2:44][CH2:45][CH2:46][C:47]1[N:51]=[CH:50][NH:49][CH:48]=1.[OH-].[Na+]>ClCCl.CN(C)C=O.O>[CH:16]1([C:8]2([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6][N:5]([C:3](=[O:4])[C@H:2]([NH:1][C:32]([NH:44][CH2:45][CH2:46][C:47]3[N:51]=[CH:50][NH:49][CH:48]=3)=[O:33])[CH2:22][C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=3)[CH2:10][CH2:9]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 66987715ethyl 1-[(R)-2-amino-3-(3,4-dichlorophenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylateHCID 178419017HCID 178419017, compound

Product 1

HCID 178468420HCID 178468420, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

60 mg (11 mmol) of ethyl 1-[(R)-2-amino-3-(3,4-dichlorophenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate and 29 mg (0.12 mmol) of para-nitrophenyl chloroformate are dissolved in 5 ml of dichloromethane. The mixture is stirred for 1 hour at room temperature and the solution is then poured into water and extracted with dichloromethane. The organic phase is dried over sodium sulfate, filtered and concentrated. The colourless oil obtained is diluted in 5 ml of dimethylformamide, the mixture is heated to 80° C., and 18 mg (0.12 mmol) of histamine are added and the solution is stirred for 5 minutes at 80° C. and overnight at room temperature. The reaction is stopped by adding aqueous 1N sodium hydroxide solution and the organic compounds are extracted with dichloromethane. The organic phase is washed with water and then dried over sodium sulfate, filtered and concentrated. The oil obtained is chromatographed on silica gel (eluent: 90/10 DCM/MeOH). 25 mg of ethyl 4-cyclohexyl-1-((R)-3-(3,4-dichlorophenyl)-2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-propionyl)piperidine-4-carboxylate in the form of a colourless oil are obtained in a yield of 38%.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe colourless oil obtained
  6. temperaturethe mixture is heated to 80° C.
  7. stirringthe solution is stirred for 5 minutes at 80° C. and overnight at room temperature
  8. extractionthe organic compounds are extracted with dichloromethane
  9. washThe organic phase is washed with water
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe oil obtained
  14. customis chromatographed on silica gel (eluent: 90/10 DCM/MeOH)

Sources & evidence

ORD record
ord-d9a65fc73684467ab6f8ffaab11beac6
Source dataset
uspto-grants-2015_02
Patent number
US08962846B2

Reaction notes

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