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

HRID 1811748Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811748
[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]

Komponenten

8

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a95b3fe80cab4813a4c1771513c17c14
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362236B2

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