Citric Acid → HCID 178468424, compound

HRID 333457Notes

Reaction equation

HRID 333457 reaction equation
[CH:1]1([C:7]2([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:12][CH2:11][N:10]([C:13](=[O:27])[C@H:14]([N:24]=[C:25]=[S:26])[CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:33][CH2:34][CH2:35][C:36]1[N:40]=[CH:39][NH:38][CH:37]=1.N12CCCN=C1CCCCC2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH:1]1([C:7]2([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:12][CH2:11][N:10]([C:13](=[O:27])[C@H:14]([NH:24][C:25]([NH:33][CH2:34][CH2:35][C:36]3[N:40]=[CH:39][NH:38][CH:37]=3)=[S:26])[CH2:15][C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)[CH2:9][CH2:8]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86659211ethyl 4-cyclohexyl-1-[(R)-2-isothiocyanato-3-(4-methoxyphenyl)propionyl]piperidine-4-carboxylateHCID 178419017HCID 178419017, compound

Product 1

HCID 178468424HCID 178468424, compoundYield 53.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 400 mg (0.87 mmol) of ethyl 4-cyclohexyl-1-[(R)-2-isothiocyanato-3-(4-methoxy-phenyl)propionyl]piperidine-4-carboxylate in 5 mL of DMF are added 97 mg (0.87 mmol) of histamine and then 0.130 mL (0.87 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene. The reaction medium is stirred for 2 hours and then hydrolysed by adding aqueous 5% citric acid solution. The organic compounds are extracted with dichloromethane. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 80/20 CH2Cl2/MeOH). 265 mg of ethyl 4-cyclohexyl-1-[(R)-2-{3-[2-(1H-imidazol-4-yl)ethyl]thioureido}-3-(4-methoxyphenyl)propionyl]piperidine-4-carboxylate in the form of a pale yellow powder are obtained in a yield of 53%.

Workup

  1. extractionThe organic compounds are extracted with dichloromethane
  2. dry with materialThe organic phase is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product obtained
  6. customis chromatographed on silica gel (eluent: 80/20 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-c3912b260c854574a3fc60733d37a476
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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