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

HRID 873025노트

반응식

HRID 873025 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 61538Palladium, di-mu-chlorobis(eta3-2-propenyl)di-촉매HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c2ae9fadd86844fa9018acd6936bd807
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975403B2

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