2,4-Dichloroaniline → 5-Cyclopropyl-6-(2,4-dichloro-phenylamino)-pyridine-2-carboxylic acid methyl ester

HRID 631951

반응식

HRID 631951 반응식
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH:36]2[CH2:38][CH2:37]2)=[C:32](Cl)[N:31]=1)=[O:29].[Cl:40][C:41]1[CH:47]=[C:46]([Cl:48])[CH:45]=[CH:44][C:42]=1[NH2:43].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([CH:36]2[CH2:38][CH2:37]2)=[C:32]([NH:43][C:42]2[CH:44]=[CH:45][C:46]([Cl:48])=[CH:47][C:41]=2[Cl:40])[N:31]=1)=[O:29]

참가 물질

7

반응물 4

HCID 111232,4-DichloroanilineHCID 11430Potassium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 866747356-Chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl ester

생성물 1

HCID 710873965-Cyclopropyl-6-(2,4-dichloro-phenylamino)-pyridine-2-carboxylic acid methyl ester수율 39%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매2회

실험 절차

A solution of palladium(II)acetate (4.24 mg, 18.9 μmol) and 2-(dicyclohexylphosphino) biphenyl (13.2 mg, 37.8 μmol) in dioxane (1.9 ml) under an argon atmosphere was stirred for 10 min at ambient temperature and subsequently added to a suspension of 6-chloro-5-cyclopropyl-pyridine-2-carboxylic acid methyl ester (100 mg, 472 μmol), 2,4-dichloroaniline (76.6 mg, 472 μmol) and potassium carbonate (1.31 g, 9.45 mmol) in dioxane (3.24 ml) under an argon atmosphere. The yellow suspension was heated to reflux and stirred for 20 h. The reaction mixture was poured into 20 mL ice/brine and extracted with i-PrOAc (2×50 mL). The combined organic layers were washed with ice/brine (1×50 mL), dried over sodium sulfate and concentrated in vacuo to give a brown oil. The crude product was purified by flash chromatography (silica gel, 4 g, 0% to 10% heptane/iPrOAc) to give the title compound (62 mg, 39%) as light brown liquid, MS (EI): m/e=337.2 [M+H]+.

후처리

  1. temperatureThe yellow suspension was heated
  2. temperatureto reflux
  3. extractionextracted with i-PrOAc (2×50 mL)
  4. washThe combined organic layers were washed with ice/brine (1×50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customThe crude product was purified by flash chromatography (silica gel, 4 g, 0% to 10% heptane/iPrOAc)

출처 및 근거

ORD 기록
ord-23631272b9a94c8994da0e4afc864e3b
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321727B2

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