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Pyridine → 4-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid pentafluorophenyl ester

HRID 917786
Notes
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Reaction equation

HRID 917786 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:11]([C:18]([OH:20])=[O:19])=[CH:12][N:13]([CH3:17])[C:14](=[O:16])[CH:15]=2)=[C:5]([F:21])[CH:4]=1)#[CH:2].FC(F)(F)C(O[C:27]1[C:32]([F:33])=[C:31]([F:34])[C:30]([F:35])=[C:29]([F:36])[C:28]=1[F:37])=O.N1C=CC=CC=1>CN(C=O)C>[F:33][C:32]1[C:27]([O:19][C:18]([C:11]2[C:10]([NH:9][C:6]3[CH:7]=[CH:8][C:3]([C:1]#[CH:2])=[CH:4][C:5]=3[F:21])=[CH:15][C:14](=[O:16])[N:13]([CH3:17])[CH:12]=2)=[O:20])=[C:28]([F:37])[C:29]([F:36])=[C:30]([F:35])[C:31]=1[F:34]
ParticipantsProcedureSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 1049PyridineHCID 4327891Pentafluorophenyl TrifluoroacetateHCID 114603454-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid

Product 1

HCID 865963824-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid pentafluorophenyl ester

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Procedure

4-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (0.70 g, 2.44 mmol) was reacted with pentafluorophenyl trifluoroacetate (1.30 mL, 7.36 mmol) in the presence of pyridine (0.60 mL) in DMF. The solution was allowed to stir at room temperature for 15 hours, to afford the 4-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid pentafluorophenyl ester which was reacted directly with 2-aminoethanol (0.74 mL, 12.20 mmol) that is stirred at room temperature for 4 hours. The resulting precipitate was filtered and purified by column chromatography on silica gel (5% MeOH/CH2Cl2 as eluant) to give 4-(4-Ethynyl-2-fluoro-phenylamino)-1-methyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (2-hydroxy-ethyl)-amide as a yellow solid (0.24 g, 30%). 1H NMR [(CD3)2SO, 400 MHz] δ 10.27 (s, 1H), 8.41 (t, 1H), 8.13 (s, 1 H), 7.48 (dd, J=10.2, 1.8 Hz, 1H), 7.40 (dd, J=8.6 Hz, 1H), 7.31 (dd, J=8.5 Hz, 1H), 5.73 (s, 1H), 4.76 (t, 1 H, OH), 4.24 (s, 1H), 3.51 (t, J=4.9 Hz, 2H), 3.35 (s, 3H), 3.25 (t, J=8.3 Hz, 2H). (APCI+) calcd for C17H16FN3O3 329.33 (M+1), found 330.1.

Sources & evidence

ORD record
ord-d5e6a7c9526b440cab697b0c6cf2a7a1
Source dataset
uspto-grants-2007_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07273877B2

Reaction notes

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