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

HRID 1093857Notes

Reaction equation

HRID 1093857 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:63]=[CH:62][CH:61]=[CH:60][C:52]=1[O:53][CH:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1>CN(C=O)C.O>[Cl:50][C:51]1[CH:63]=[CH:62][CH:61]=[CH:60][C:52]=1[O:53][CH:54]1[CH2:59][CH2:58][N:57]([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])[CH2:56][CH2:55]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 167325894-(2-Chlorophenoxy)piperidine hydrochlorideHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acid

Product 1

HCID 442352691-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amideYield 62.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (170 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) (55 mg, 0.29 mmol) in DMF (5 mL) followed by HOBt (43 mg, 0.32 mmol) and EDCI (140 mg, 0.7 mmol). After 2 minutes of stirring, 4-(2-chloro-phenoxy)-piperidine hydrochloride (98 mg, 0.32 mmol) was added and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with cold water and the precipitate was collected. The precipitate was purified by recrystallisation from a mixture of 20% EtOAc in hexane (15 mL) and MeOH (0.1 mL) to afford the 80 mg (62.5% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 439.15, 98.75%. 1H NMR (300 MHz, DMSO-d6): δ 8.4 (s, 1H), 8.3 (s, 1H), 8.08 (t, 1H), 7.8 (d, 2H), 7.6 (t, 2H), 7.48 (m, 2H), 7.34 (m, 2H), 7.1 (t, 1H), 4.8 (m, 1H), 4.2 (d, 2H), 3.8 (t, 2H), 3.6 (t, 2H), 2.0 (d, 2H), 1.8 (d, 2H).

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature overnight
  2. customthe precipitate was collected
  3. customThe precipitate was purified by recrystallisation from a mixture of 20% EtOAc in hexane (15 mL) and MeOH (0.1 mL)

Sources & evidence

ORD record
ord-6bf9f414c8434cc48709cd5ab3ca0b11
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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