Sodium hydride → HCID 22281927, 화합물

HRID 1062805노트

반응식

HRID 1062805 반응식
[NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([O:8][CH2:9][CH2:10][OH:11])[C:3]=1[C:12]1[CH:20]=[CH:19][C:15]2[O:16][CH2:17][O:18][C:14]=2[CH:13]=1.[H-].[Na+].[Cl:23][C:24]1[CH:25]=[N:26][C:27](S(C)(=O)=O)=[N:28][CH:29]=1.[Cl-].[NH4+]>O1CCCC1>[O:16]1[C:15]2[CH:19]=[CH:20][C:12]([C:3]3[C:4]([O:8][CH2:9][CH2:10][O:11][C:27]4[N:28]=[CH:29][C:24]([Cl:23])=[CH:25][N:26]=4)=[N:5][N:6]([CH3:7])[C:2]=3[NH2:1])=[CH:13][C:14]=2[O:18][CH2:17]1

참가 물질

6

반응물 4

HCID 24758Sodium hydride3회HCID 25517Ammonium ChlorideHCID 27277255-Chloro-2-methanesulfonylpyrimidine2회HCID 22281969HCID 22281969, 화합물

생성물 1

HCID 22281927HCID 22281927, 화합물수율 91.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a −78° C. cooled solution of 2-{[5-amino-4-(1,3-benzodioxol-5-yl)-1-methyl-1H-pyrazol-3-yl]oxy}-1-ethanol (710 mg) (Preparation 45) in anhydrous tetrahydrofurane (25 ml) under an atmosphere of nitrogen, was added sodium hydride (60% dispersion in oil, 113 mg) and the mixture was stirred for 10 minutes at this temperature before 5-chloro-2-(methylsulfonyl)pyrimidine (543 mg) was added in one portion and the mixture was stirred overnight at room temperature. The TLC indicated an incomplete reaction so the mixture was cooled to −78° C. and another portion of sodium hydride (60% dispersion in oil, 100 mg) was added. The mixture was stirred for 12 h at room temperature. Again, the TLC indicated an incomplete reaction. The mixture was cooled again to −78° C. and sodium hydride (60% dispersion in oil, 100 mg) was added. After 10 minutes at this temperature, 5-chloro-2-(methylsulfonyl)pyrimidine (200 mg) was added in one portion. The reaction was stirred overnight at room temperature. An aqueous saturated solution of ammonium chloride (1 ml) was carefully added before the reaction mixture was concentrated under reduced pressure. The residue was dissolved in a mixture of water (20 ml) and dichloromethane (20 ml). The phases were separated and the aqueous phase was extracted with dichloromethane (2×20 ml). The combined organic fractions were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica, 30 g) eluted with dichloromethane:methanol (95:5) yielding the title compound as a colourless oil (910 mg).

후처리

  1. additionwas added in one portion
  2. customan incomplete reaction so the mixture
  3. temperaturewas cooled to −78° C.
  4. stirringThe mixture was stirred for 12 h at room temperature
  5. customan incomplete reaction
  6. temperatureThe mixture was cooled again to −78° C.
  7. stirringThe reaction was stirred overnight at room temperature
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionThe residue was dissolved in a mixture of water (20 ml) and dichloromethane (20 ml)
  10. customThe phases were separated
  11. extractionthe aqueous phase was extracted with dichloromethane (2×20 ml)
  12. dry with materialThe combined organic fractions were dried over sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by column chromatography (silica, 30 g)
  15. washeluted with dichloromethane:methanol (95:5)

출처 및 근거

ORD 기록
ord-f3d3e23d47834b90a41cf20aac964af1
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06962923B2

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