Hydrochloric Acid → 3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine

HRID 1262409

반응식

HRID 1262409 반응식
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([S:30][CH3:31])=[N:28]2)=[CH:23][CH:22]=1.Cl.[NH2:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCCC1.C(O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:31][S:30][C:27]1[N:26]=[CH:25][C:24]2=[CH:23][CH:22]=[C:21]([C:38]3[CH:39]=[C:34]([NH2:33])[CH:35]=[CH:36][CH:37]=3)[N:29]2[N:28]=1

참가 물질

10

반응물 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27632413-Aminophenylboronic acid hydrochlorideHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

생성물 1

HCID 667126823-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine수율 39.1%

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 702Ethanol용매HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

Palladium Acetate (0.37 g, 0.0016 mol) and Triphenylphosphine (0.54 g, 0.0020 mol) were dissolved in Tetrahydrofuran (25 mL) and the mixture was allowed to stir at room temperature for 10 minutes. 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (1.95 g, 0.00799 mol) and 3-Aminophenylboronic acid hydrochloride (2.84 g, 0.0164 mol) were added followed by 2.00 M of Sodium carbonate in Water (20.0 mL, 0.0400 mol) and Ethanol (25 mL). The reaction mixture was then heated at 75° C. and was allowed to stir overnight. The reaction mixture was diluted with water (40 mL), cooled and acidified with 12M HCl, then washed twice with EtOAc (50 mL). The org. wash was extracted with 3M HCl (3×30 mL) and the combined aq. extr. washed with EtOAc (2×50 mL). The aq. was then basified with 5N NaOH to pH 9, then extracted with DCM (4×30 mL). The DCM extr. was washed with brine (50 mL) and dried over sodium sulfate before conc. in vacuo. The residue was applied to a 25 g ISCO preload cartridge and purified on the ISCO (40 g, 5-40% EtOAc:Hex). Clean product was isolated from select fractions to afford 3-(2-Methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenylamine (0.80 g, 39%).

후처리

  1. temperatureThe reaction mixture was then heated at 75° C.
  2. stirringto stir overnight
  3. temperaturecooled
  4. washwashed twice with EtOAc (50 mL)
  5. washwash
  6. extractionwas extracted with 3M HCl (3×30 mL)
  7. washwashed with EtOAc (2×50 mL)
  8. extractionextracted with DCM (4×30 mL)
  9. washwas washed with brine (50 mL)
  10. dry with materialdried over sodium sulfate before conc. in vacuo
  11. custompurified on the ISCO (40 g, 5-40% EtOAc:Hex)
  12. customClean product was isolated from select fractions

출처 및 근거

ORD 기록
ord-70b54cd2ca4941d1a9f7d5639a0d0cbd
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08471005B2

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