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

HRID 1811748Notes

Reaction equation

HRID 1811748 reaction equation
[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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-a95b3fe80cab4813a4c1771513c17c14
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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