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

HRID 2353629ノート

反応式

HRID 2353629 の反応式
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]

参加物

11

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 5

HCID 178418476HCID 178418476、化合物触媒2 回HCID 702Ethanol溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-eccfe853f08946b8a275b1c4d8df147f
出典データセット
uspto-grants-2010_07
特許番号
US07750003B2

反応ノート

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