Tetrahydrofuran → 2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [1-(2-ethyl-2-hydroxy-1,1-dimethyl-butyl)-1H-imidazol-4-yl]-amide

HRID 553193Notes

Reaction equation

HRID 553193 reaction equation
CO[C:3](=[O:31])[C:4]([N:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:30])[CH:14]([NH:18][C:19](=[O:29])[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[CH2:15][CH2:16][CH3:17])[N:9]=[CH:8]1)([CH3:6])[CH3:5].[CH2:32]([Li])[CH3:33].O1CC[CH2:37][CH2:36]1>>[CH2:36]([C:3]([OH:31])([CH2:32][CH3:33])[C:4]([N:7]1[CH:11]=[C:10]([NH:12][C:13](=[O:30])[CH:14]([NH:18][C:19](=[O:29])[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[CH2:15][CH2:16][CH3:17])[N:9]=[CH:8]1)([CH3:6])[CH3:5])[CH3:37]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 115972762-(4-{2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoylamino}-imidazol-1-yl)-2-methyl-propionic acid methyl esterHCID 178506846HCID 178506846, compound

Product 1

HCID 117123922-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [1-(2-ethyl-2-hydroxy-1,1-dimethyl-butyl)-1H-imidazol-4-yl]-amide

Procedure

To a solution of 2-(4-{2-[2-(3,5-difluoro-phenyl)-acetylamino]-pentanoylamino}-imidazol-1-yl)-2-methyl-propionic acid methyl ester (1 equiv) in tetrahydrofuran at −0° C. is added ethyl lithium (5 equiv., 0.5 M benzene/cyclohexane) dropwise. The reaction is stirred for 30 min., quenched with water, and extracted with methylene chloride. The solvent is dried, concentrated, and purified by silica gel chromatography to afford the title compound: C13 NMR (100 MHz, CDCl3) 9.0, 9.3, 14.0, 18.9, 24.5, 25.2, 27.3, 27.5, 36.0, 43.0, 53.1, 65.9, 102.5, 102.8, 103.0, 107.2, 112.4, 112.6, 112.7, 133.3, 136.3, 138.6, 164.3, 164.5, 169.0, 169.1; MS m/z 465.3 (M+1).

Workup

  1. customquenched with water
  2. extractionextracted with methylene chloride
  3. customThe solvent is dried
  4. concentrationconcentrated
  5. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-3c859f2f0c184781b8856669d44dc3d8
Source dataset
uspto-grants-2011_05
Patent number
US07951958B2

Reaction notes

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