Trimethylsilylacetylene → HCID 23630909, compound

HRID 917714Notes

Reaction equation

HRID 917714 reaction equation
[F:1][C:2]1[CH:19]=[C:18](I)[CH:17]=[CH:16][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH2:15])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.[Si:21]([C:25]#[CH:26])([CH3:24])([CH3:23])[CH3:22]>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:19]=[C:18]([C:26]#[C:25][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:17]=[CH:16][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH2:15])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 11338183HCID 11338183, compound

Product 1

HCID 23630909HCID 23630909, compoundYield 100%

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)-1-methyl-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}-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a pale yellow solid (100%), used directly in the next step. 1H NMR [(CD3)2SO, 400 MHz] δ 10.66 (s, 1H), 8.38 (s, 1H), 7.92 (br s, 1H), 7.50 (t, J=8.5 Hz, 1H), 7.48 (br s, 1H), 7.42 (dd, J=11.5, 1.8 Hz, 1H), 7.30 (dd, J=8.3, 1.4 Hz, 1H), 5.73 (s, 1H), 3.38 (s, 3H), 0.23 (s, 9H). HRMS (EI+) calcd C18H20FN3O2Si (M+) 357.1309, found 357.1308.

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-b84d654787c3495c913b104225ece8ac
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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