2,4-Dichloroquinazoline → HCID 58972436, compound

HRID 2264405Notes

Reaction equation

HRID 2264405 reaction equation
[Br-].[S:2]1[CH:6]=[CH:5][N:4]=[C:3]1[Zn+].[Cl:8][C:9]1[N:18]=[C:17](Cl)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:8][C:9]1[N:18]=[C:17]([C:3]2[S:2][CH:6]=[CH:5][N:4]=2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=1

Participants

5

Reactant 2

HCID 2528862,4-DichloroquinazolineHCID 178419763HCID 178419763, compound2×

Product 1

HCID 58972436HCID 58972436, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
110 °C

Procedure

To a 0.5 M solution of 2-thiazolyl zinc bromide in THF (12.1 mL, 6.03 mmol, 1.2 equiv; commercially available from Aldrich) under Ar was added 2,4-dichloro-quinazoline (1.0 g, 5.02 mmol, 1.0 equiv) and tetrakis(triphenylphosphine) palladium(0) (232.2 mg, 0.20 mmol, 0.04 equiv) and the reaction mixture heated by microwave irradiation to 110° C. After 30 min additional 2-thiazolyl zinc bromide in THF (12.1 mL, 6.03 mmol, 1.2 equiv) was added and the reaction mixture heated to 110° C. for another 30 min. The crude reaction mixture was concentrated by evaporation under reduced pressure and the residue purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 0.36 g (29%) of the title compound. MS (ISP): 248.3 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated to 110° C. for another 30 min
  2. customThe crude reaction mixture
  3. concentrationwas concentrated by evaporation under reduced pressure
  4. customthe residue purified by silica column chromatography
  5. washeluting with a gradient of heptane/ethyl acetate providing 0.36 g (29%) of the title compound

Sources & evidence

ORD record
ord-bc795c0175bc41e5929868efba6e2637
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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