1,1'-Carbonyldiimidazole → 3,4-Difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamide

HRID 1793018Notes

Reaction equation

HRID 1793018 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][CH2:22][O:23][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)=[CH:15][C:14]=2[F:30])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=[O:6].C1N=CN(C(N2C=NC=C2)=O)C=1.[NH2:43][O:44][CH2:45][CH2:46][OH:47]>>[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][CH2:22][OH:23])=[CH:15][C:14]=2[F:30])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([NH:43][O:44][CH2:45][CH2:46][OH:47])=[O:7].[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][CH2:22][O:23][CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)=[CH:15][C:14]=2[F:30])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([NH:43][O:44][CH2:45][CH2:46][OH:47])=[O:6]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 3014186Ethanol, 2-(aminooxy)-HCID 220256423,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic Acid

Product 2

HCID 102874233,4-Difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamideHCID 220256283,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}-N-(2-hydroxyethoxy)benzamide

Procedure

The title compound was prepared by reaction of 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by column chromatography on silica gel (50% EtOAc/PE as eluant) to give 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}-N-(2-hydroxyethoxy)benzamide as a viscous transparent oil which was immediately dissolved in EtOH and treated with 1 M HCl according to the general procedure of Example 10, Step D. Purification of the resulting oil was carried out by filtration through a plug of silica gel (EtOAc as eluant) to give 3,4-difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamide as a pale yellow crystalline solid (51%); m.p. (EtOAc/Et2O) 126–129° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.82 (br s, 1 H), 8.85 (br s, 1 H), 7.45–7.39 (m, 1 H), 7.25–7.17 (m, 2H), 7.07 (dd, J=8.3, 1.4 Hz, 1 H), 6.78 (dd, J=8.8, 8.8, 4.7 Hz, 1 H), 4.88 (t, J=5.6 Hz, 1 H), 4.73 (br s, 1 H), 3.85 (t, J=4.8 Hz, 2 H), 3.59–3.53 (m, 4 H), 2.53 (t, J=6.9 Hz, 1 H). Anal. calcd. for C19H17F3N2O4.0.25Et2O: C, 58.2; H, 4.8; N, 6.8. Found C, 58.1; H, 4.8; N, 7.1.

Workup

  1. custompurified by column chromatography on silica gel (50% EtOAc/PE as eluant)

Sources & evidence

ORD record
ord-56cd40aec004470d9237abd900b00daa
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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