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

HRID 408474노트

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HRID 408474 반응식
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

참가 물질

8

반응물 4

HCID 312ChlorideHCID 81531DiisopropylethylamineHCID 27343362,6-Difluorophenylboronic acidHCID 199886952-Chloro-8-methoxyquinazoline

생성물 1

HCID 583868032-(2,6-Difluorophenyl)-8-methoxyquinazoline

시약·촉매·용매 3

HCID 178418807HCID 178418807, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매

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온도
130 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-52d06594b5f44f619c4684a1d851b1ed
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759338B2

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