(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester → (4R,9aR)-6-Cyano-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11922

반응식

HRID 11922 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15](Br)=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cu][C:24]#[N:25]>O1CCOCC1.[C-]#N.C([N+](CC)(CC)CC)C.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([C:24]#[N:25])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 2

HCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2회HCID 178418546HCID 178418546, 화합물

생성물 1

HCID 69556656(4R,9aR)-6-Cyano-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester수율 98.4%

시약·촉매·용매 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 3014735Tetraethylammonium cyanide촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

To a solution of 0.20 g (0.54 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) in 5 ml dioxane were added 195.0 mg (2.17 mmol) copper(I)cyanide, 22.5 mg (22 μmol) tris(dibenzylideneacetone)dipalladium(0), 48.2 mg (87 μmol) 1,1′-bis(diphenylphosphino)ferrocene and 0.13 g (0.81 mmol) tetraethylammonium cyanide and the suspension was heated to reflux and stirred for 1.5 h. The mixture was cooled to room temperature, filtered and the filtrate was washed successively with aqueous saturated sodium bicarbonate solution, aqueous 10% citric acid solution, brine, dried over magnesium sulfate, filtered and evaporated. The residue was immediately purified by flash column chromatography on silica gel (0.032–0.063 mm) to afford the desired compound as a colorless foam (98.4%).

후처리

  1. temperaturethe suspension was heated
  2. temperatureto reflux
  3. filtrationfiltered
  4. washthe filtrate was washed successively with aqueous saturated sodium bicarbonate solution, aqueous 10% citric acid solution, brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was immediately purified by flash column chromatography on silica gel (0.032–0.063 mm)

출처 및 근거

ORD 기록
ord-22ed86cfb9ec4e0589ebac4532874db4
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07098337B2

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