Lithium Hydroxide → N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamide

HRID 2381776Notes

Reaction equation

HRID 2381776 reaction equation
[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14](Br)=[N:13][C:12]=1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:18](N(CC)C(C)C)(C)[CH3:19].C[Si](C#C)(C)C.[OH-].[Li+]>C1(C)C=CC=CC=1.C(OCC)(=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>[CH2:1]([NH:8][C:9]([C:11]1[S:15][C:14]([C:18]#[CH:19])=[N:13][C:12]=1[CH3:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 579593962-Bromo-4-methyl-thiazole-5-carboxylic acid benzylamide

Product 1

HCID 73213266N-benzyl-2-ethynyl-4-methylthiazole-5-carboxamideYield 93%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of N-benzyl-2-bromo-4-methylthiazole-5-carboxamide (0.10 g, 0.32 mmol) in anhydrous toluene (1 mL) was added copper(I) iodide (0.001 g, 0.006 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.005 g, 0.006 mmol), and N,N-diisopropylethylamine (0.17 mL, 0.97 mmol). The reaction mixture was degassed and the reaction flask was filled with nitrogen followed by the addition of trimethylsilylacetylene (0.089 mL, 0.64 mmol). The reaction mixture was heated at 35° C. for 3 hours, cooled to ambient temperature and treated with 1 M aqueous lithium hydroxide (1.0 mL) for 5 minutes, diluted with ethyl acetate (10 mL), washed with water (3 mL) and brine (3 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate:hexanes, 1:1) to afford the title compound as a brown solid (0.035 g, 93%): 1H NMR (300 MHz, CDCl3) δ 7.43-7.21 (m, 5H), 6.17 (t, J=5.7 Hz, 1H), 4.56 (d, J=5.7 Hz, 2H), 3.49 (s, 1H), 2.65 (s, 3H); MS (ES+) m/z 257.2 (M+1).

Workup

  1. customThe reaction mixture was degassed
  2. additionthe reaction flask was filled with nitrogen
  3. temperaturecooled to ambient temperature
  4. washwashed with water (3 mL) and brine (3 mL)
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ethyl acetate:hexanes, 1:1)

Sources & evidence

ORD record
ord-4b963e15520f4d18af7f06ed71b2bad1
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

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