1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57874435, compound

HRID 1093860Notes

Reaction equation

HRID 1093860 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.[F:50][C:51]1[CH:52]=[C:53]([CH:59]=[C:60]([C:62]([F:65])([F:64])[F:63])[CH:61]=1)[O:54][CH:55]1[CH2:58][NH:57][CH2:56]1>CN(C=O)C>[F:50][C:51]1[CH:52]=[C:53]([CH:59]=[C:60]([C:62]([F:64])([F:63])[F:65])[CH:61]=1)[O:54][CH:55]1[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]1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66591819[(1-phenyl-1H-imidazole-4-carbonyl)-amino]-acetic acidHCID 665922143-(3-Fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride

Product 1

HCID 57874435HCID 57874435, compoundYield 31.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (143 mg, 1.1 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) (68 g, 0.27 mmol) in DMF (2 mL) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol). After 2 minutes of stirring, 3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (75 mg, 0.27 mmol) was added and it was stirred overnight at ambient temperature. Partitioning with cold water and ethyl acetate and concentration of the organic layer after drying over sodium sulfate afforded a residue which was purified by preparative HPLC to give 40 mg (31.4% Yield) of 1-phenyl-1H-imidazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 463, 99.18%. 1H NMR (300 MHz, DMSO-d6): δ 8.44 (d, 1H), 8.34 (d, 1H), 8.2 (t, 1H), 7.8 (d, 2H), 7.56 (t, 2H), 7.44 (m, 1H), 7.34 (d, 1H), 7.12 (m, 2H), 5.25 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.3 (m, 1H), 3.9 (m, 3H).

Workup

  1. additionwas added
  2. stirringit was stirred overnight at ambient temperature
  3. customPartitioning with cold water and ethyl acetate and concentration of the organic layer
  4. dry with materialafter drying over sodium sulfate
  5. customafforded a residue which
  6. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-6a768278bcb24b458239c9b29c1761d4
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…