Citric Acid → HCID 178468425, compound

HRID 1855669Notes

Reaction equation

HRID 1855669 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.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:47]1[CH:51]=[C:50]([CH2:52][CH2:53]CN)[N:49]=[CH:48]1.[N:56]12CCCN=C1CCCC[CH2:57]2.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:56][CH2:57][CH:52]([C:50]3[N:49]=[CH:48][NH:47][CH:51]=3)[CH3:53])=[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 178510940HCID 178510940, compound

Product 1

HCID 178468425HCID 178468425, compoundYield 26.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 65 mg (0.141 mmol) of ethyl 4-cyclohexyl-1-[(R)-2-isothiocyanato-3-(4-methoxy-phenyl)propionyl]piperidine-4-carboxylate in 5 ml of DMF are added 50 mg (0.141 mmol) of 3-(1H-imidazol-4-yl)propylamine bis(trifluoroacetate) (cf. preparation 4-2) and then 0.063 ml (0.425 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). 22 mg of ethyl 4-cyclohexyl-1-[(R)-2-{3-[2-(1H-imidazol-4-yl)propyl]thioureido}-3-(4-methoxy-phenyl)propionyl]piperidine-4-carboxylate in the form of a pale yellow powder are obtained in a yield of 26%.

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-bf885925527245ca8e76bff3df731f5b
Source dataset
uspto-grants-2015_02
Patent number
US08962846B2

Reaction notes

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