Water → HCID 59224649, compound

HRID 1811706Notes

Reaction equation

HRID 1811706 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.[C:16]([O:20][C:21](=[O:39])[C:22]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[C:25]([CH3:37])=[CH:24][C:23]=1[CH3:38])([CH3:19])([CH3:18])[CH3:17]>O1CCOCC1.C(OCC)(=O)C>[C:16]([O:20][C:21](=[O:39])[C:22]1[CH:27]=[C:26]([C:4]2[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([NH2:1])[N:3]=2)[C:25]([CH3:37])=[CH:24][C:23]=1[CH3:38])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 962WaterHCID 655222-Amino-4,6-dichloropyrimidineHCID 516892Sodium BicarbonateHCID 59224661HCID 59224661, compound

Product 1

HCID 59224649HCID 59224649, compoundYield 70.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

Commercially available 2-amino-4,6-dichloropyrimidine (460 mg, 2.8 mmol), palladium dichloride-diphenylphosphinoferrocene dichloromethane complex (98 mg, 0.12 mmol), sodium bicarbonate (471 mg, 5.61 mmol), 1,4-dioxane (4.5 ml), and water (2.5 ml) were placed in a reaction vessel. The resulting mixture was stirred at 80° C. for 10 minutes. 2,4-Dimethyl-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)benzoic acid tert-butyl ester (620 mg, 1.8 mmol) obtained in Step 3 above that was dissolved in 1,4-dioxane (4.5 ml) was added dropwise to the mixture. The resulting mixture was stirred at 80° C. for 19 hours. The reaction solution was diluted with ethyl acetate (150 ml), and washed with water (80 ml) three times and then with a saturated aqueous sodium chloride solution (80 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate (30 g). 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=10:1 to 5:1) to yield 5-(2-amino-6-chloropyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (Compound 1-1) (422 mg) as a white solid material.

Workup

  1. additionwas added dropwise to the mixture
  2. stirringThe resulting mixture was stirred at 80° C. for 19 hours
  3. washwashed with water (80 ml) three times
  4. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate (30 g)
  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=10:1 to 5:1)

Sources & evidence

ORD record
ord-2b8e4cb7055f49c08d975c40d3d847d4
Source dataset
uspto-grants-2013_01
Patent number
US08362236B2

Reaction notes

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