Sodium Carbonate → 2-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]aniline

HRID 2353629Notes

Reaction equation

HRID 2353629 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.C([O-])(=O)C.[K+].CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.Cl[C:34]1[N:39]=[C:38]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][C@@H:41]2[CH3:46])[CH:37]=[C:36]([CH2:47][S:48]([CH3:51])(=[O:50])=[O:49])[N:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.O.C(O)C>[CH3:9][C:4]1[CH:3]=[C:2]([C:34]2[N:39]=[C:38]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][C@@H:41]3[CH3:46])[CH:37]=[C:36]([CH2:47][S:48]([CH3:51])(=[O:49])=[O:50])[N:35]=2)[CH:8]=[CH:7][C:5]=1[NH2:6]

Participants

11

Reactant 5

HCID 10340Sodium CarbonateHCID 114234-Bromo-2-methylanilineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 575473562-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine

Product 1

HCID 593801402-methyl-4-[4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidin-2-yl]anilineYield 14.3%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-2-methylaniline (1.00 g, 5.37 mmol), potassium acetate (1.59 g, 16.1 mmol) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.64 g, 6.45 mmol) were dissolved in 1,4-dioxane (20 mL) and the solution degassed for 5 minutes. Dichlorobis(triphenylphosphine)palladium (264 mg, 0.32 mmol) was added and the reaction stirred at 90° C. for 4 hours. 2-Chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine (1.65 g, 5.37 mmol), ethanol (1.5 mL), 2M sodium carbonate aqueous solution (3 mL) and dichlorobis(triphenylphosphine)palladium (264 mg) were added. The reaction was maintained at 90° C. for 18 hours then allowed to cool to room temperature. Water (15 mL) and ethyl acetate (15 mL) were added and the mixture was filtered to remove the insoluble impurities. The phases were separated and the aqueous layer extracted with a second portion of ethyl acetate (15 mL). The combined organics were dried (MgSO4) and concentrated in vacuo. The residue was chromatographed on silica, eluting with 0-3% methanol in DCM, to give the desired compound as a beige foam (290 mg).

Workup

  1. customthe solution degassed for 5 minutes
  2. temperatureThe reaction was maintained at 90° C. for 18 hours
  3. temperatureto cool to room temperature
  4. filtrationthe mixture was filtered
  5. customto remove the insoluble impurities
  6. customThe phases were separated
  7. extractionthe aqueous layer extracted with a second portion of ethyl acetate (15 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was chromatographed on silica
  11. washeluting with 0-3% methanol in DCM

Sources & evidence

ORD record
ord-eccfe853f08946b8a275b1c4d8df147f
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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