Propargyl alcohol → 4-(Methylthio)-6-methoxy-7-(3-hydroxyprop-1-ynyl)quinazoline

HRID 2233266Notes

Reaction equation

HRID 2233266 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)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[CH2:23]([OH:26])[C:24]#[CH:25]>CN(C)C=O.C(N(CC)CC)C>[CH3:1][S:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([C:25]#[C:24][CH2:23][OH:26])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1

Participants

5

Reactant 2

HCID 7859Propargyl alcoholHCID 867610994-(Methylthio)-6-methoxy-7-(trifluoromethanesulphonyloxy)quinazoline

Product 1

HCID 686771564-(Methylthio)-6-methoxy-7-(3-hydroxyprop-1-ynyl)quinazolineYield 17%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6228DimethylformamideSolvent

Procedure

4-(methylthio)-6-methoxy-7-(trifluoromethanesulphonyloxy)quinazoline (1.0 g, 2.82 mmol) in dimethylformamide (30 ml) was reacted with propargyl alcohol (0.51 ml, 8.75 mmol) in the presence of bisdichloro(triphenylphosphine) palladium (100 mg, 0.14 mmol) copper (I) iodide (40 mg) and triethylamine (1.7 ml, 0.0124 mmol) at 90° C. for 2.5 hours under argon. The solvent was evaporated in vacuo, water and hydrochloric acid (2.0 N) were added, and the mixture was extracted with ethyl acetate. Purification by flash chromatography on silica gel, eluting with 7.5% methanol in dichloromethane, yielded 4-(methylthio)-6-methoxy-7-(3-hydroxyprop-1-ynyl)quinazoline (122 mg, 17% yield):

Workup

  1. customThe solvent was evaporated in vacuo, water and hydrochloric acid (2.0 N)
  2. additionwere added
  3. extractionthe mixture was extracted with ethyl acetate
  4. customPurification by flash chromatography on silica gel
  5. washeluting with 7.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-42c6ac856b084e63aa63b595414e1d06
Source dataset
uspto-grants-2010_05
Patent number
US07709479B1

Reaction notes

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