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

HRID 2353629노트

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HRID 2353629 반응식
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]

참가 물질

11

반응물 5

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

생성물 1

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

시약·촉매·용매 5

HCID 178418476HCID 178418476, 화합물촉매2회HCID 702Ethanol용매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-eccfe853f08946b8a275b1c4d8df147f
출처 데이터셋
uspto-grants-2010_07
특허 번호
US07750003B2

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