Trimethylsilylacetylene → HCID 58962863, compound

HRID 917708Notes

Reaction equation

HRID 917708 reaction equation
[F:1][C:2]1[CH:21]=[C:20](I)[CH:19]=[CH:18][C:3]=1[NH:4][C:5]1[C:6]([C:12]([NH:14][CH2:15][CH2:16][OH:17])=[O:13])=[CH:7][NH:8][C:9](=[O:11])[CH:10]=1.[Si:23]([C:27]#[CH:28])([CH3:26])([CH3:25])[CH3:24]>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:21]=[C:20]([C:28]#[C:27][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:19]=[CH:18][C:3]=1[NH:4][C:5]1[C:6]([C:12]([NH:14][CH2:15][CH2:16][OH:17])=[O:13])=[CH:7][NH:8][C:9](=[O:11])[CH:10]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 11774389HCID 11774389, compound

Product 1

HCID 58962863HCID 58962863, compoundYield 72%

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)-6-oxo-1,6-dihydro-3-pyridinecarboxamide was reacted with TMS-acetylene 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-[(trimethylsilyl)ethynyl]anilino}-N-(2-hydroxyethyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide as an off-white solid (72%), used directly in the next step. 1H NMR [(CD3)2SO, 400 MHz] δ 11.45 (br s, 1H), 10.45 (s, 1H), 8.50 (t, J=5.4 Hz, 1H), 7.96 (s, 1H), 7.48 (t, J=8.4 Hz, 1H), 7.42 (dd, J=11.5, 1.8 Hz, 1H), 7.30 (dd, J=8.3, 1.4 Hz, 1H), 5.65 (s, 1H), 4.71 (t, J=5.7 Hz, 1H), 3.49 (q, J=5.9 Hz, 2H), 3.29-3.24 (m, 2H), 0.24 (s, 9H). HRMS (FAB+) calcd C19H23FN3O3Si (MH+) 388.1493, found 388.1488.

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-baf4bec785dc4830a21372a9ce6f97e8
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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