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

HRID 1093858Notes

Reaction equation

HRID 1093858 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.FC(F)(F)C(O)=O.[F:56][C:57]([F:72])([F:71])[C:58]1[CH:70]=[CH:69][CH:68]=[CH:67][C:59]=1[O:60][CH:61]1[CH2:66][CH2:65][NH:64][CH2:63][CH2:62]1>CN(C=O)C.O>[O:27]=[C:25]([N:64]1[CH2:63][CH2:62][CH:61]([O:60][C:59]2[CH:67]=[CH:68][CH:69]=[CH:70][C:58]=2[C:57]([F:56])([F:71])[F:72])[CH2:66][CH2:65]1)[CH2:24][NH:23][C:21]([C:19]1[N:18]=[CH:17][N:16]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:20]=1)=[O:22]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acidHCID 866346354-(2-Trifluoromethyl-phenoxy)-piperidine trifluoracetate

Product 1

HCID 578744641-phenyl-1H-imidazole-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amideYield 58.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (236 mg, 1.826 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) (100 mg, 0.4 mmol) in DMF (5 mL) followed by HOBt (60.5 mg, 0.4 mmol) and EDCI (195 mg, 1.02 mmol). After 2 minutes of stirring, 4-(2-trifluoromethyl-phenoxy)-piperidine trifluoroacetate (126 mg, 0.45 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 filtered. The precipitate was purified by recrystallisation from a mixture of 20% EtOAc in hexane (15 mL) and MeOH (0.1 mL) to afford 113 mg (58.2% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 473, 96.85%. 1H NMR (300 MHz, DMSO-d6): δ 8.4 (s, 1H), 8.3 (s, 1H), 8.08 (t, 1H), 7.8 (d, 2H), 7.68-7.6 (t, 2H), 7.6 (t, 2H), 7.4-7.34 (m, 2H), 7.14 (t, 1H), 5.0 (m, 1H), 4.2 (d, 2H), 3.7-3.4 (m, 4H), 2.1 (d, 2H), 1.8 (d, 2H).

Workup

  1. stirringthe resulting mixture was stirred at ambient temperature overnight
  2. filtrationthe precipitate was filtered
  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-25ec62fe12054f3591a2e4426233d9c2
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…