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

HRID 1262409

反応式

HRID 1262409 の反応式
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

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 702Ethanol溶媒HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-70b54cd2ca4941d1a9f7d5639a0d0cbd
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

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