Water → HCID 59224651, compound

HRID 1811712Notes

Reaction equation

HRID 1811712 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.C(=O)(O)[O-].[Na+].O.[CH3:16][O:17][C:18](=[O:38])[C:19]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[C:22]([CH3:34])=[CH:21][C:20]=1[O:35][CH2:36][CH3:37]>O1CCOCC1.C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:16][O:17][C:18](=[O:38])[C:19]1[CH:24]=[C:23]([C:4]2[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([NH2:1])[N:3]=2)[C:22]([CH3:34])=[CH:21][C:20]=1[O:35][CH2:36][CH3:37]

Participants

8

Reactant 4

HCID 962WaterHCID 655222-Amino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 59224645HCID 59224645, compound

Product 1

HCID 59224651HCID 59224651, compoundYield 65.3%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

2-Amino-4,6-dichloropyrimidine (246 mg, 1.5 mmol), bis(triphenylphosphine) palladium dichloride (53 mg, 0.07 mmol), sodium bicarbonate (252 mg, 3.0 mmol), 1,4-dioxane (2.5 ml), and water (1.5 ml) were placed in a reaction vessel. The resulting mixture was stirred at 80° C. for 10 minutes. To this mixture, 2-Ethoxy-4-methyl-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzoic acid methyl ester (320 mg, 1.0 mmol) obtained in Step 4 above was added dropwise after dissolving in 1,4-dioxane (2.5 ml). The resulting mixture was stirred at 80° C. for 20 hours. The reaction solution was diluted with ethyl acetate (100 ml), and washed three times with water (40 ml), and then with a saturated aqueous sodium chloride solution (40 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate (10 g). After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=2:1) to yield 5-(2-amino-6-chloropyrimidin-4-yl)-2-ethoxy-4-methylbenzoic acid methyl ester (Compound 1-3) (210 mg) as a yellow solid material.

Workup

  1. stirringThe resulting mixture was stirred at 80° C. for 20 hours
  2. washwashed three times with water (40 ml)
  3. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate (10 g)
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-8ec7ec39009d4bae8a17115e650baecd
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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