1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093865Notes

Reaction equation

HRID 1093865 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([N:16]2[CH:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[N:18]=[CH:17]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[Cl:50][C:51]1[CH:62]=[CH:61][CH:60]=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][NH:56][CH2:55]1>CN(C=O)C.O>[Cl:50][C:51]1[CH:62]=[CH:61][CH:60]=[CH:59][C:52]=1[O:53][CH:54]1[CH2:58][CH2:57][N:56]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:19]2[N:18]=[CH:17][N:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:22])[CH2:55]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 450754773-(2-Chlorophenoxy)pyrrolidine hydrochlorideHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid

Product 1

HCID 578744121-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amideYield 34.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (167.9 mg, 1.3 mmol) was added to a stirred solution of [(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid (prepared from Intermediate 68 by means of Step 3 of the General Scheme) (80 mg, 0.32 mmol) in DMF (2 mL) followed by HOBt (48.3 mg, 0.35 mmol) and EDCI (124 mg, 0.65 mmol). After 2 minutes of stirring, 3-(2-chloro-phenoxy)-pyrrolidine hydrochloride (prepared by the method used for the synthesis of Intermediate 72) (76 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate, and concentrated under reduced pressure. Purification by recrystallisation from a mixture of DCM in hexane afforded 48 mg (34.7% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 425, 93.15%. 1H NMR (300 MHz, DMSO-d6): δ 8.4 (s, 1H), 8.3 (s, 1H), 8.1-8.0 (t, 1H), 7.8-7.7 (t, 2H), 7.5-7.4 (m, 2H), 7.4-7.2 (m, 2H), 7.06-7.0 (m, 1H), 5.3-5.1 (d, 1H), 4.2-4.0 (m, 2H), 4.0-3.5 (m, 4H), 2.3-2.2 (m, 1H), 2.2-2.0 (m, 1H).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification
  7. customby recrystallisation
  8. additionfrom a mixture of DCM in hexane

Sources & evidence

ORD record
ord-56e31f5beb8444a89ac026246f7b53cb
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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