2-Methyl-3-butyn-2-ol → 4-(Methylthio)-7-(3-hydroxy-3-methylbut-1-ynyl)quinazoline

HRID 2233265Notes

Reaction equation

HRID 2233265 reaction equation
[CH3:1][S:2][C:3]1[C:12]2[C:7](=[CH:8][C:9](OS(C(F)(F)F)(=O)=O)=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1.[CH3:21][C:22]([OH:26])([C:24]#[CH:25])[CH3:23].C(N(CC)CC)C>CN(C)C=O.[Cu]I>[CH3:1][S:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([C:25]#[C:24][C:22]([OH:26])([CH3:23])[CH3:21])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 857840454-(Methylthio)-7-(trifluoromethanesulphonyloxy)quinazoline

Product 1

HCID 686768364-(Methylthio)-7-(3-hydroxy-3-methylbut-1-ynyl)quinazolineYield 174.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

4-(Methylthio)-7-(trifluoromethanesulphonyloxy)quinazoline (592 mg, 1.82 mmol) in dimethylformamide (20 ml) was reacted with 2-methyl-3-butyn-2-ol (0.53 ml, 0.54 mmol) in the presence of bis dichloro(triphenylphosphine)palladium (64 mg, 0.091 mmol), copper (I) iodide (20 mg) and triethylamine (1.1 ml, 0.8 mmol), at 90° C. for 2.5 hours. The solvent was removed in vacuo, aqueous hydrochloric acid (2N) was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulphate and the solvents were evaporated in vacuo. Purification by flash chromatography on silica gel, eluting with isohexane/ethyl acetate (55:45), yielded, 4-(methylthio)-7-(3-hydroxy-3-methylbut-1-ynyl)quinazoline (243 mg, 51% yield):

Workup

  1. customThe solvent was removed in vacuo, aqueous hydrochloric acid (2N)
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulphate
  6. customthe solvents were evaporated in vacuo
  7. customPurification by flash chromatography on silica gel
  8. washeluting with isohexane/ethyl acetate (55:45)
  9. customyielded

Sources & evidence

ORD record
ord-c25752486bd542dcbe529de59fcf65e2
Source dataset
uspto-grants-2010_05
Patent number
US07709479B1

Reaction notes

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