1,2-Dichloroethane → HCID 178450005, compound

HRID 333426Notes

Reaction equation

HRID 333426 reaction equation
[NH:1]1[CH:5]=[C:4]([CH2:6][CH2:7][NH:8][C:9](=[O:24])[NH:10][CH:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:12]([OH:14])=O)[N:3]=[CH:2]1.FC(F)(F)C(O)=O.[CH2:32]([O:36][C:37]1([CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)[CH2:33][CH2:34][CH3:35].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH2:32]([O:36][C:37]1([CH:43]2[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]2)[CH2:38][CH2:39][N:40]([C:12](=[O:14])[CH:11]([NH:10][C:9]([NH:8][CH2:7][CH2:6][C:4]2[N:3]=[CH:2][NH:1][CH:5]=2)=[O:24])[CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[CH2:41][CH2:42]1)[CH2:33][CH2:34][CH3:35]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 311Citric AcidHCID 757711-HydroxybenzotriazoleHCID 669879764-Butoxy-4-cyclohexylpiperidine trifluoroacetateHCID 178490381HCID 178490381, compound

Product 1

HCID 178450005HCID 178450005, compoundYield 22.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 69 mg (0.21 mmol) of 2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)-propanoic acid (cf. preparation 2-3) dissolved in 2 mL of DMF is added a solution of 71 mg (0.20 mmol) of 4-butoxy-4-cyclohexylpiperidine trifluoroacetate in 1.5 mL of DMF, 44 mg (0.23 mmol) of EDC and 33 mg (0.24 mmol) of HOBt. After 2 hours 30 minutes, the reaction medium is hydrolysed with aqueous 2% citric acid solution and then extracted with dichloromethane. The organic phase is then washed with aqueous 1N sodium hydroxide solution. The organic phase is dried over MgSO4, filtered and concentrated. This oil is chromatographed on silica gel (eluent: 8/2 DCM/MeOH). 25 mg of 1-[2-(4-butoxy-4-cyclohexylpiperidin-1-yl)-1-(4-methoxy-benzyl)-2-oxoethyl]-3-[2-(1H-imidazol-4-yl)ethyl]urea are obtained in a yield of 22%.

Workup

  1. extractionextracted with dichloromethane
  2. washThe organic phase is then washed with aqueous 1N sodium hydroxide solution
  3. dry with materialThe organic phase is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis oil is chromatographed on silica gel (eluent: 8/2 DCM/MeOH)

Sources & evidence

ORD record
ord-768b353424ab487e829cb0a3784ba18c
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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