Diisopropylamine → HCID 178468421, compound

HRID 333454Notes

Reaction equation

HRID 333454 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].ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.FC(F)(F)[C:46]([OH:48])=O.FC(F)(F)C(O)=O.[NH:58]1[CH:62]=[C:61]([CH2:63][CH2:64][CH2:65][NH2:66])[N:60]=[CH:59]1.C(NC(C)C)(C)C.[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:46]([NH:66][CH2:65][CH2:64][CH2:63][C:61]3[N:60]=[CH:59][NH:58][CH:62]=3)=[O:48])[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

9

Reactant 5

HCID 7912DiisopropylamineHCID 14798Sodium HydroxideHCID 821294-Nitrophenyl chloroformateHCID 66987715ethyl 1-[(R)-2-amino-3-(3,4-dichlorophenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylateHCID 178510940HCID 178510940, compound

Product 1

HCID 178468421HCID 178468421, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

0.07 g (0.15 mmol) of ethyl 1-[(R)-2-amino-3-(3,4-dichlorophenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate and 34 mg (0.17 mmol) of para-nitrophenyl chloroformate are dissolved in 5 mL of dichloromethane. The mixture is stirred for 2 hours 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 to dryness. The colourless oil obtained is diluted in 5 mL of dimethylformamide, the mixture is heated to 80° C., and 57 mg (0.16 mmol) of 3-(1H-imidazol-4-yl)propylamine bis(trifluoroacetate) are added with 0.05 mL (0.3 mmol) of diisopropylamine. The solution is stirred for 5 minutes at 80° C. and for 16 hours at room temperature. The reaction is stopped by adding aqueous 1N sodium hydroxide solution and then extracted with dichloromethane. The organic phase is washed with water and then dried over sodium sulfate, filtered and evaporated to dryness. The oil obtained is chromatographed (eluent: 90/10 DCM/MeOH). 40 mg of ethyl 4-cyclohexyl-1-((R)-3-(3,4-dichlorophenyl)-2-{3-[3-(1H-imidazol-4-yl)propyl]ureido}-propionyl)piperidine-4-carboxylate in the form of a colourless oil are obtained in a yield of 44%.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  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 for 16 hours at room temperature
  8. extractionextracted with dichloromethane
  9. washThe organic phase is washed with water
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated to dryness
  13. customThe oil obtained
  14. customis chromatographed (eluent: 90/10 DCM/MeOH)

Sources & evidence

ORD record
ord-dfcf260a2e864aaf9c87633838f9ac25
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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