1,1'-Carbonyldiimidazole → 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide

HRID 2181445Notes

Reaction equation

HRID 2181445 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][O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[CH:15][C:14]=2[F:29])=[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.[NH2:42][O:43][CH2:44][CH2:45][OH:46]>>[F:29][C:14]1[CH:15]=[C:16]([C:19]#[C:20][CH2:21][O:22][CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)[CH:17]=[CH:18][C:13]=1[NH2:12].[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]#[C:20][CH2:21][O:22][CH:23]3[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[CH:15][C:14]=2[F:29])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([NH:42][O:43][CH2:44][CH2:45][OH:46])=[O:7]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 3014186Ethanol, 2-(aminooxy)-HCID 220256553,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid

Product 2

HCID 220256372-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilineHCID 220256673,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamideYield 69%

Procedure

The title compound was prepared from reaction of 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]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-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide as a white solid (69%) which was used directly in the next step. 1H NMR [400 MHz, (CD3)2SO] δ 11.80 (br s, 1 H), 8.87 (br s, 1 H), 7.46-7.39 (m, 1 H), 7.31 (dd, J=12.2, 1.8 Hz, 1 H), 7.28-7.20 (m, 1 H), 7.14 (dd, J=8.3, 1.6 Hz, 1 H), 6.79 (ddd, J=8.8, 8.8, 4.7 Hz, 1 H), 4.80 (br s, 1 H), 4.46 (d, J=16.1 Hz, 1 H), 4.36 (d, J=16.0 Hz, 1 H), 3.84 (t, J=4.8 Hz, 2 H), 3.75 (ddd, J=11.5, 8.6, 3.3 Hz, 2 H), 3.55 (t, J=4.8 Hz, 2 H), 3.51-3.44 (m, 2 H), 1.76-1.60 (m, 2 H), 1.55-1.42 (m, 4 H). HRMS (EI+) calcd. for C23H23F3N2O5 464.1559 (M+), found 464.1558.

Workup

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

Sources & evidence

ORD record
ord-9c3bb79d57f94d03a351679ed7c8d654
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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