Chloride → 2-(2,6-Difluorophenyl)-8-methoxyquinazoline

HRID 408474Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH3:13])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1B(O)O.CCN(C(C)C)C(C)C.[Cl-]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C(O)C.C1(C)C=CC=CC=1>[F:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[C:16]=1[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[C:5]([O:12][CH3:13])[CH:6]=[CH:7][CH:8]=2)[N:3]=1

Participants

Conditions

Temperature: 130 °C

Procedure

2-chloro-8-methoxyquinazoline (1.0 eq), 2,6-difluorophenylboronic acid (1.5 eq), and DIPEA (3 eq) was mixed with toluene and ethanol (1:1, 0.5M) in a microwave vial. The reaction mixture was degassed by anhydrous N2 stream for 5 min followed by the addition of Pd(dppf)Cl2-DCM (0.1 eq). The reaction mixture was stirred at 130° C. for 30 min in microwave. Solvents were removed under reduced pressure. The crude product was purified by column (ethyl acetate:hexanes=1:1) to give the mixture of starting material chloride and desired product. The mixture was treated with 1N HCl in 1,4-dioxane. Solvents were removed under reduced pressure. The residue was dissolved in ethyl acetate (150 mL), and washed with NaHCO3, brine, then dried over MgSO4, filtered, and evaporated under reduced pressure to give crude product, which was purified by column (ethyl acetate:hexanes=1:1) to yield 2-(2,6-difluorophenyl)-8-methoxyquinazoline (46%). LC/MS (m/z): 273.0 (MH+), Rt=0.78.

Workup

customThe reaction mixture was degassed by anhydrous N2 stream for 5 min
customSolvents were removed under reduced pressure
customThe crude product was purified by column (ethyl acetate:hexanes=1:1)
customto give

Sources & evidence

ORD record: ord-52d06594b5f44f619c4684a1d851b1ed
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759338B2

Reaction notes

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