Carbonate Ion → 1-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-indazol-4-amine

HRID 551426

반응식

HRID 551426 반응식
CC1C=CC(S(O[CH2:12][C:13]2([C:16]([F:19])([F:18])[F:17])[CH2:15][O:14]2)(=O)=O)=CC=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([NH2:36])[C:30]=3[CH:29]=[N:28]2)=[CH:23][CH:22]=1.[Bi](Cl)(Cl)Cl.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-]>ClCCl.C(Cl)(Cl)Cl.O1CCCC1.[Bi](Cl)(Cl)Cl.CN(C=O)C>[F:20][C:21]1[CH:22]=[CH:23][C:24]([N:27]2[C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([NH:36][CH2:12][C:13]4([C:16]([F:17])([F:18])[F:19])[CH2:15][O:14]4)[C:30]=3[CH:29]=[N:28]2)=[CH:25][CH:26]=1

참가 물질

11

반응물 5

HCID 19660Carbonate IonHCID 24591Bismuth trichlorideHCID 81531DiisopropylethylamineHCID 24809749(2-(Trifluoromethyl)oxiran-2-yl)methyl 4-methylbenzenesulfonateHCID 249380581-(4-Fluorophenyl)-1H-indazol-4-amine

생성물 1

HCID 249380561-(4-fluorophenyl)-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-indazol-4-amine수율 59.1%

시약·촉매·용매 5

HCID 24591Bismuth trichloride촉매HCID 6212Chloroform용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

[2-(trifluoromethyl)-2-oxiranyl]methyl 4-methylbenzenesulfonate (6.14 g, 20.75 mmol) and 1-(4-fluorophenyl)-1H-indazol-4-amine (4.73 g, 20.75 mmol) in dry dichloromethane (5 ml) were stirred for 5 min. Bismuth chloride (654 mg, 2.07 mmol) was added and the mixture stirred at room temperature over the weekend. More bismuth chloride (0.33 g, 1.05 mmol) was then added and the mixture stirred overnight. The reaction was finally stirred overnight under nitrogen (to reduce the volume of DMF). There was no further progress on leaving for a further night. The reaction mixture was then diluted with chloroform (200 ml) and tetrahydrofuran (50 ml). N,N-Diisopropylethylamine (0.54 ml, 3.11 mmol) was added followed by polymer supported carbonate resin (Fluka, ca. 3.5 mmoles carbonate/g resin, 11.91 g) and the mixture stirred overnight. More THF (30 ml) was then added followed after 2 hours by some 4 A molecular sieves. After a further 3 hours LCMS indicated the reaction to be complete and the mixture was filtered. The filtrate was washed with water, the aqueous phase was back-extracted with dichloromethane and the combined organic phases were dried and evaporated to give crude product which was purified by silica gel chromatography using the Flashmaster II (2×100 g cartridges) eluting with a 0 to 50% dichloromethane:ethyl acetate gradient to give the title compound (4.31 g).

후처리

  1. stirringthe mixture stirred overnight
  2. customon leaving for a further night
  3. stirringthe mixture stirred overnight
  4. waitfollowed after 2 hours by some 4
  5. waitAfter a further 3 hours LCMS indicated
  6. customthe reaction
  7. filtrationthe mixture was filtered
  8. washThe filtrate was washed with water
  9. extractionthe aqueous phase was back-extracted with dichloromethane
  10. customthe combined organic phases were dried
  11. customevaporated
  12. customto give crude product which
  13. customwas purified by silica gel chromatography
  14. washeluting with a 0 to 50% dichloromethane

출처 및 근거

ORD 기록
ord-b42ab2c801bc40188d392c1cf60a3bcb
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07947727B2

연결된 노트

불러오는 중…