Methylamine hydrochloride → 1-(4-Fluoro-phenyl)-6-methylamino-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

HRID 1677712노트

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HRID 1677712 반응식
[CH3:1][NH:2][S:3]([C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]([C:14]2[C:15]3[CH:16]=[N:17][N:18]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[C:19]=3[CH:20]=[C:21](Br)[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4].Cl.[CH3:34][NH2:35].CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:1][NH:2][S:3]([C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]([C:14]2[C:15]3[CH:16]=[N:17][N:18]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[C:19]=3[CH:20]=[C:21]([NH:35][CH3:34])[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4]

참가 물질

6

반응물 3

HCID 6364545Methylamine hydrochlorideHCID 23676156Sodium t-butoxideHCID 444698036-Bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

생성물 1

HCID 444684461-(4-Fluoro-phenyl)-6-methylamino-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

A mixture of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide (0.05 g, 0.1 mmol), methylamine hydrochloride (0.01 g, 0.2 mmol), palladium(II) acetate di-t-butylbiphenylphosphine (0.005 g, 0.01 mmol) and sodium t-butoxide (0.03 g, 0.25 mmol) was charged in a sealed tube with dioxane (5 mL). The tube was capped, degassed with argon for 5 minutes and warmed at 90° C. for 2 hours. The reaction was cooled to room temperature and filtered through diatomaceous earth, and diluted with water (5 mL) and ethyl acetate (20 mL). The organic layer was separated and washed with brine (10 mL), dried over sodium sulfate, and concentrated. The residue was purified by reversed-phase HPLC eluting with a gradient of 5-100% CH3CN in water. The desired fractions were combined and diluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL). The organic layer was separated, dried over sodium sulfate and concentrated to afford the title compound.

후처리

  1. customThe tube was capped
  2. customdegassed with argon for 5 minutes
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered through diatomaceous earth
  5. additiondiluted with water (5 mL) and ethyl acetate (20 mL)
  6. customThe organic layer was separated
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by reversed-phase HPLC
  11. washeluting with a gradient of 5-100% CH3CN in water
  12. additiondiluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL)
  13. customThe organic layer was separated
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated

출처 및 근거

ORD 기록
ord-4235cf88959b44bf98e2be0b0518645b
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08008327B2

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