Sodium Hydroxide → HCID 178468422, compound

HRID 333447Notes

Reaction equation

HRID 333447 reaction equation
[NH2:1][C@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][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].[NH4+].[OH-].[NH2:46][CH2:47][CH2:48][C:49]1[N:53]=[CH:52][NH:51][CH:50]=1.[OH-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH:16]1([C:8]2([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@H:2]([NH:1][C:32]([NH:46][CH2:47][CH2:48][C:49]3[N:53]=[CH:52][NH:51][CH:50]=3)=[O:33])[CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[CH2:6][CH2:7]2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 66987937ethyl 1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylateHCID 178419017HCID 178419017, compound

Product 1

HCID 178468422HCID 178468422, compoundYield 47.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 2.35 g (5.64 mmol) of ethyl 1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate dissolved in 25 mL of DCM immersed in a bath of cold water are added 1.25 g (6.21 mmol) of 4-nitrophenyl chloroformate. After warming to room temperature, the reaction medium is stirred for 1 hour. The reaction is stopped by adding aqueous NH4OH solution and the organic compounds are extracted with DCM. The organic phase is then washed with water and then dried over MgSO4, filtered and concentrated. The crude product obtained is dissolved in 25 mL of DMF at 80° C., and 0.70 g (6.3 mmol) of histamine is then added. After 15 minutes, the reaction is stopped by adding aqueous 1N sodium hydroxide solution and the organic compounds are extracted with DCM. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 86/14 DCM/MeOH). 1.48 g of ethyl 4-cyclohexyl-1-[(R)-2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propionyl]piperidine-4-carboxylate in the form of a white powder are obtained in a yield of 47%.

Workup

  1. extractionthe organic compounds are extracted with DCM
  2. washThe organic phase is then washed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product obtained
  7. waitAfter 15 minutes
  8. extractionthe organic compounds are extracted with DCM
  9. dry with materialThe organic phase is dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product obtained
  13. customis chromatographed on silica gel (eluent: 86/14 DCM/MeOH)

Sources & evidence

ORD record
ord-be967b85e24f42ce8483086873baa6e2
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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