1,2-Dichloroethane → N-cyclopropyl-N-{1-[2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propionyl]piperidin-4-yl}-propionamide

HRID 333422Notes

Reaction equation

HRID 333422 reaction equation
[CH:1]1([N:4]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[C:5](=[O:8])[CH2:6][CH3:7])[CH2:3][CH2:2]1.[NH:15]1[CH:19]=[C:18]([CH2:20][CH2:21][NH:22][C:23](=[O:38])[NH:24][CH:25]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=2)[C:26](O)=[O:27])[N:17]=[CH:16]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[CH:1]1([N:4]([CH:9]2[CH2:14][CH2:13][N:12]([C:26](=[O:27])[CH:25]([NH:24][C:23]([NH:22][CH2:21][CH2:20][C:18]3[N:17]=[CH:16][NH:15][CH:19]=3)=[O:38])[CH2:29][C:30]3[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=3)[CH2:11][CH2:10]2)[C:5](=[O:8])[CH2:6][CH3:7])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 12050271N-cyclopropyl-N-piperidin-4-ylpropionamideHCID 178490381HCID 178490381, compound

Product 1

HCID 178459999N-cyclopropyl-N-{1-[2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propionyl]piperidin-4-yl}-propionamideYield 8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

100 mg (0.51 mmol) of N-cyclopropyl-N-piperidin-4-ylpropionamide, 170 mg (0.51 mmol) of 2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propanoic acid (cf. preparation 2-3), 108 mg (0.56 mmol) of EDC and 76 mg (0.56 mmol) of HOBT are dissolved in 5 mL of DMF under nitrogen. The mixture is stirred at room temperature overnight, and the solution is then washed with aqueous 5% citric acid solution and extracted with ethyl acetate. The organic phase is washed with aqueous 1N NaOH solution and then dried and evaporated. The crude product obtained is purified by preparative HPLC (conditions cf. page 38). 2 mg of N-cyclopropyl-N-{1-[2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propionyl]piperidin-4-yl}-propionamide are obtained in a yield of 8%.

Workup

  1. washthe solution is then washed with aqueous 5% citric acid solution
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with aqueous 1N NaOH solution
  4. customdried
  5. customevaporated
  6. customThe crude product obtained
  7. customis purified by preparative HPLC (conditions cf. page 38)

Sources & evidence

ORD record
ord-c1cf3dab7f384f2c99ac67fc06b84656
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

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