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

HRID 408474ノート

反応式

HRID 408474 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

反応条件

温度
130 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-52d06594b5f44f619c4684a1d851b1ed
出典データセット
uspto-grants-2014_06
特許番号
US08759338B2

反応ノート

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