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

HRID 1811748ノート

反応式

HRID 1811748 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a95b3fe80cab4813a4c1771513c17c14
出典データセット
uspto-grants-2013_01
特許番号
US08362236B2

反応ノート

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