Dimethylacetamide → HCID 66647033、化合物

HRID 217593ノート

反応式

HRID 217593 の反応式
[NH2:1][C:2]1[C:3]([F:20])=[C:4]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16](Br)[CH:17]=3)[NH:12][CH:11]=2)=[O:9])[CH:5]=[CH:6][CH:7]=1.[CH3:21][N:22](C)C(=O)C>[Zn].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-]#N.[Zn+2].[C-]#N.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].O>[NH2:1][C:2]1[C:3]([F:20])=[C:4]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:21]#[N:22])[CH:17]=3)[NH:12][CH:11]=2)=[O:9])[CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 2

HCID 31374DimethylacetamideHCID 58368906(3-Amino-2-fluoro-phenyl)-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone

生成物 1

HCID 66647033HCID 66647033、化合物収率 67.7%

試薬・触媒・溶媒 5

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
120 °C

実験手順

To (3-amino-2-fluoro-phenyl)-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (22, 1.080 g, 3.232 mmol) in a vial, N,N-dimethylacetamide (2.90 mL, 31.2 mmol) was added. The suspension was degassed by bubbling with argon and zinc powder (0.032 g, 0.48 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.0568 g, 0.102 mmol), zinc cyanide (0.223 g, 1.90 mmol), and tris(dibenzylideneacetone)dipalladium (0) (0.053 g, 0.052 mmol) were added at room temperature under argon. The mixture was heated to 120° C., resulting in most of the solid dissolving, and the mixture was heated at 120° C. for 2 hours, then cooled to 100° C. and 8 mL of water was added and the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate and saturated sodium chloride in water. The organic layer was washed with water and brine, then dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was suspended in acetonitrile and sonicated for 30 minutes, after which the precipitated material was collected by filtration to provide the desired compound as a tan solid (23, 613 mg). Additional material was recovered from the filtrate by silica gel chromatography eluting with ethyl acetate and hexanes, the appropriate fractions were combined and the solvent removed to provide an additional 42 mg. MS (ESI) [M+H+]+=280.9.

後処理

  1. customThe suspension was degassed
  2. additionwere added at room temperature under argon
  3. customresulting in most of the solid
  4. dissolutiondissolving
  5. temperaturethe mixture was heated at 120° C. for 2 hours
  6. temperaturecooled to 100° C.
  7. temperaturethe reaction mixture cooled to room temperature
  8. extractionThe reaction mixture was extracted with ethyl acetate and saturated sodium chloride in water
  9. washThe organic layer was washed with water and brine
  10. dry with materialdried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum
  13. customsonicated for 30 minutes
  14. filtrationafter which the precipitated material was collected by filtration

出典と根拠

ORDレコード
ord-8f3cb1103f9742618e3cccf63003b1a2
出典データセット
uspto-grants-2012_06
特許番号
US08198273B2

反応ノート

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