Propargyl alcohol → HCID 11199166, compound

HRID 917702Notes

Reaction equation

HRID 917702 reaction equation
[F:1][C:2]1[CH:22]=[C:21](I)[CH:20]=[CH:19][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][CH2:16][CH2:17][OH:18])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.[CH2:24]([OH:27])[C:25]#[CH:26]>C1COCC1.CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:22]=[C:21]([C:26]#[C:25][CH2:24][OH:27])[CH:20]=[CH:19][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][CH2:16][CH2:17][OH:18])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 11189634HCID 11189634, compound

Product 1

HCID 11199166HCID 11199166, compoundYield 79%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

4-(2-Fluoro-4-iodoanilino)-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide was reacted with propargyl alcohol in the presence of CuI, (Ph3P)2PdCl2 and TEA in THF/DMF (1:1) as for example 2. The residue resulting from removal of the reaction solvents under reduced pressure was purified by column chromatography on silica gel (10% MeOH/CH2Cl2 as eluant) to give 4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethyl)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a cream solid (79%). 1H NMR [(CD3)2SO, 400 MHz] δ 10.26 (s, 1H), 8.44 (t, J=5.4 Hz, 1H), 8.30 (s, 1H), 7.48 (t, J=8.4 Hz, 1H), 7.38 (dd, J=11.6, 1.8 Hz, 1H), 7.27 (dd, J=8.3, 1.4 Hz, 1H), 5.70 (s, 1H), 5.35 (t, J=5.9 Hz, 1H), 4.76 (t, J=5.7 Hz, 1H), 4.30 (d, J=6.0 Hz, 2H), 3.50 (q, J=5.8 Hz, 2H), 3.38 (s, 3H), 3.31-3.26 (m, 2H). LCMS (APCI+) calcd for C18H18FN3O4 360 (MH+), found 360.

Workup

  1. customThe residue resulting from removal of the reaction solvents under reduced pressure
  2. customwas purified by column chromatography on silica gel (10% MeOH/CH2Cl2 as eluant)

Sources & evidence

ORD record
ord-ff1b3931676842cc856f70c41b2e3cd3
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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