1,1'-Carbonyldiimidazole → 3,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamide

HRID 2181435Notes

Reaction equation

HRID 2181435 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[CH2:20])=[CH:15][C:14]=2[F:21])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:34][O:35][CH2:36][CH2:37][OH:38]>>[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]=[CH2:20])=[CH:15][C:14]=2[F:21])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([NH:34][O:35][CH2:36][CH2:37][OH:38])=[O:7]

Participants

4

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 3014186Ethanol, 2-(aminooxy)-HCID 220256413,4-Difluoro-2-[(2-fluoro-4-vinylphenyl)amino]benzoic acid

Product 1

HCID 102369933,4-Difluoro-2-(2-fluoro-4-vinylanilino)-N-(2-hydroxyethoxy)benzamideYield 78%

Procedure

The title compound was prepared from reaction of the product of Example 4, Step A, 3,4-difluoro-2-[(2-fluoro-4-vinylphenyl)amino]benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by flash column chromatography on silica gel (10% EtOAc/hexanes) to give 3,4-difluoro-2-[(2-fluoro-4-vinylphenyl)amino]-N-(2-hydroxyethoxy)benzamide as a crystalline white solid (78%); m.p. (EtOAc/hexanes) 134-138° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.85 (br s, 1 H), 8.82 (br s, 1 H), 7.45-7.38 (m, 1 H), 7.37 (dd, J=12.9, 1.8 Hz, 1 H), 7.21-7.15 (m, 1H), 7.14 (dd, J=8.4, 1.7 Hz, 1 H), 6.83 (td, J=8.7, 4.8 Hz, 1 H), 6.65 (dd, J=17.6, 10.8 Hz, 1 H), 5.73 (d, J=17.9 Hz, 1 H), 5.18 (d, J=11.1 Hz, 1 H), 4.70 (br s, 1 H), 3.85 (t, J=4.8 Hz, 1 H), 3.56 (t, J=4.8 Hz, 2 H). Anal. Calcd for C17H15F3N2O3: C, 58.0; H, 4.3; N, 8.0. Found C, 57.6; H, 4.6; N, 8.1.

Workup

  1. custompurified by flash column chromatography on silica gel (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-80db97edd5b34c2bb62397c4ea94c83c
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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