Sodium hydride → (S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester

HRID 1436570노트

반응식

HRID 1436570 반응식
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][CH:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[Na+].[CH3:39][S:40]([NH-:43])(=[O:42])=[O:41].[H-].[Na+].CS(N)(=O)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([NH:43][S:40]([CH3:39])(=[O:42])=[O:41])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

참가 물질

9

반응물 5

HCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 13150714Methanesulfonamide sodium saltHCID 866150062-Sec-butylamino-6-chloro-isonicotinic acid methyl ester

생성물 1

HCID 68814626(S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester수율 76.1%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

실험 절차

Add 2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (500 mg, 2.07 mmol), toluene (10 mL), tris(dibenzylideneacetone)dipalladium(0) (95 mg, 0.104 mmol), 2-(di-tert-butylphosphino)biphenyl (62 mg, 0.207 mmol), and methanesulfonamide sodium salt (363 mg, 3.11 mmol) to a sealed flask flushed with nitrogen. (Prepare methanesulfonamide sodium salt by adding sodium hydride (2.0 g, 50.0 mmol, 60% dispersion in mineral oil) slowly to a solution of methanesulfonamide (5.0 g, 52.6 mmol) and THF (80 mL) at 0° C.) Stir the mixture at room temperature overnight. Concentrate and dry the residue under vacuum. Heat and stir the sealed flask at 100° C. for 18 h. Cool to room temperature, filter through a pad of filtering agent, wash with dichloromethane, concentrate the filtrate and purify (silica gel chromatography, eluting with 20:80 to 25:75 ethyl acetate:hexanes) to give the title compound (475 mg, 76%).

후처리

  1. customflushed with nitrogen
  2. custom(Prepare methanesulfonamide sodium salt
  3. concentrationConcentrate
  4. customdry the residue under vacuum
  5. temperatureHeat
  6. stirringstir the sealed flask at 100° C. for 18 h
  7. temperatureCool to room temperature
  8. filtrationfilter through a pad
  9. filtrationof filtering agent
  10. washwash with dichloromethane
  11. concentrationconcentrate the filtrate
  12. custompurify
  13. wash(silica gel chromatography, eluting with 20:80 to 25:75 ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-8c1893059d174778be2d50a1b6c7077f
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07618978B2

반응 노트

불러오는 중…