Potassium Fluoride → 2-(5-Amino-6-benzyl-3-chloropyrazin-2-yl)-5-methoxybenzaldehyde

HRID 873025ノート

反応式

HRID 873025 の反応式
C(P(C(C)(C)C)C1N(C2C=CC=CC=2)C2C(C=1)=CC=CC=2)(C)(C)C.[NH2:25][C:26]1[C:31]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:30][C:29](Br)=[C:28]([Cl:40])[N:27]=1.[CH:41]([C:43]1[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[CH:45][C:44]=1B(O)O)=[O:42].[F-].[K+]>C1COCC1.[CH2-]C=C.[CH2-]C=C.Cl[Pd+].Cl[Pd+].O>[NH2:25][C:26]1[N:27]=[C:28]([Cl:40])[C:29]([C:44]2[CH:45]=[CH:46][C:47]([O:49][CH3:50])=[CH:48][C:43]=2[CH:41]=[O:42])=[N:30][C:31]=1[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

参加物

8

反応物 4

HCID 522689Potassium FluorideHCID 27343652-Formyl-4-methoxybenzeneboronic acidHCID 111751332-(di-tert-butylphosphino)-N-phenylindoleHCID 866706762-Amino-3-benzyl-5-bromo-6-chloropyrazine

生成物 1

HCID 866706772-(5-Amino-6-benzyl-3-chloropyrazin-2-yl)-5-methoxybenzaldehyde収率 76.9%

試薬・触媒・溶媒 3

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-触媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

Under an argon atmosphere, to a solution of allylpalladium(II) chloride dimer (160 mg, 437 μmol) in anhydrous THF (30 mL) was added 2-(di-tert-butylphosphino)-1-phenylindole (295 mg, 874 μmol) at room temperature, followed by stirring at room temperature for 10 minutes. Subsequently, to the mixture were successively added 2-amino-3-benzyl-5-bromo-6-chloropyrazine (5) (2.60 g, 8.74 mmol), 2-formyl-4-methoxyphenylboronic acid (6) (3.14 g, 17.4 mmol), potassium fluoride (2.60 g, 44.8 mmol) and water (160 μL, 8.88 mmol) at room temperature. The mixture was stirred overnight (14 hours) at room temperature without further treatment. After to this was added water, the product was extracted with ethyl acetate (×3). The combined organic extract was washed successively with water (×1) and brine (×1), and dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1) to give 2-(5-amino-6-benzyl-3-chloropyrazin-2-yl)-5-methoxybenzaldehyde (7) (2.37 g, 6.70 mmol, 76.9%) as a reddish brown solid. TLC Rf=0.27 (n-hexane/ethyl acetate=3/1); 1H NMR (500 MHz, CDCl3) δ 3.92 (s, 3H), 4.13 (s, 2H), 4.66 (s, 2H), 7.21-7.25 (m, 3H), 7.27-7.31 (m, 1H), 7.32-7.37 (m, 2H), 7.51-7.55 (m, 2H), 9.92 (s, 1H).; 13C NMR (126 MHz, CDCl3) δ 40.4, 55.7, 111.2, 120.7, 127.4, 128.4 (2C), 129.2 (2C), 132.5, 132.7, 135.7, 135.8, 137.8, 139.1, 144.1, 151.5, 160.0, 191.0.

後処理

  1. customat room temperature
  2. stirringThe mixture was stirred overnight (14 hours) at room temperature without further treatment
  3. extractionthe product was extracted with ethyl acetate (×3)
  4. extractionThe combined organic extract
  5. washwas washed successively with water (×1) and brine (×1)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration and concentration under reduced pressure
  8. customthe residue was purified by silica gel flash column chromatography (n-hexane/ethyl acetate=3/1)

出典と根拠

ORDレコード
ord-c2ae9fadd86844fa9018acd6936bd807
出典データセット
uspto-grants-2015_03
特許番号
US08975403B2

反応ノート

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