Triphenylphosphine → 5-[2-Amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2,4-dichlorobenzoic acid methyl ester

HRID 1811748노트

반응식

HRID 1811748 반응식
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[C:7]([Cl:19])=[CH:6][C:5]=1[Cl:20].[C:22]([O:26][C:27](=[O:40])[NH:28][CH2:29][CH2:30][S:31][C:32]1[CH:37]=[C:36](Cl)[N:35]=[C:34]([NH2:39])[N:33]=1)([CH3:25])([CH3:24])[CH3:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(COC)OC>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:36]2[CH:37]=[C:32]([S:31][CH2:30][CH2:29][NH:28][C:27]([O:26][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:40])[N:33]=[C:34]([NH2:39])[N:35]=2)[C:7]([Cl:19])=[CH:6][C:5]=1[Cl:20]

참가 물질

8

반응물 4

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 59224716[2-(2-Amino-6-chloropyrimidin-4-ylsulfanyl)ethyl]carbamic acid tert-butyl esterHCID 68413491Methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

생성물 1

HCID 592246575-[2-Amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2,4-dichlorobenzoic acid methyl ester수율 35%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A mixture of the crude product of 2,4-dichloro-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzoic acid methyl ester (320 mg) obtained in Step 3 of Example 2-8, [2-(2-amino-6-chloropyrimidin-4-ylsulfanyl)ethyl]carbamic acid tert-butyl ester (177 mg, 0.58 mmol) obtained in Step 1 above, palladium acetate (5 mg, 0.02 mmol), triphenylphosphine (19 mg, 0.07 mmol), 1N aqueous sodium bicarbonate solution (725 μl), and dimethoxyethane (4.4 ml) was stirred at 80° C. for 2 hours. After the reaction solution was cooled to room temperature, water was added thereto and extracted with ethyl acetate. The organic layer was sequentially washed with water and a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=3:1 to 1:1) to yield 5-[2-amino-6-(2-tert-butoxycarbonylaminoethylsulfanyl)pyrimidin-4-yl]-2,4-dichlorobenzoic acid methyl ester (96 mg).

후처리

  1. temperatureAfter the reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was sequentially washed with water
  4. dry with materiala saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate
  5. filtrationAfter filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=3:1 to 1:1)

출처 및 근거

ORD 기록
ord-a95b3fe80cab4813a4c1771513c17c14
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362236B2

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