Formic Acid → 7-bromoquinazoline

HRID 661120Notes

Reaction equation

HRID 661120 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][C:8](I)=[N:9]2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 11776TriphenylphosphineHCID 77174867HCID 77174867, compound

Product 1

HCID 111951467-bromoquinazolineYield 51.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of 7-bromo-2-iodoquinazoline (69 mg, 206 μmol), triphenylphosphine (5.4 mg, 21 μmol), and Pd(OAc)2 (3.2 mg, 14 μmol) in DMF (4.0 mL) was added TEA (72 μL, 515 μmol) and formic acid (9.5 μL, 247 μmol). The reaction mixture was stirred at 70° C. overnight. After cooling, the reaction mixture was concentrated, and the crude residue was dissolved in DCM and mixed with SiO2. The solvent was evaporated, and the residue was purified with flash column chromatography (pure DCM→3% MeOH in DCM) to obtain the desired product 7-bromoquinazoline (22 mg, 51%) as a white solid. LCMS (API-ES) m/z (%): 210.0 (100%, M++H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionthe crude residue was dissolved in DCM
  4. additionmixed with SiO2
  5. customThe solvent was evaporated
  6. customthe residue was purified with flash column chromatography (pure DCM→3% MeOH in DCM)

Sources & evidence

ORD record
ord-c6d89a5510494540ab47ba2dd3db3e49
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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