Potassium Phosphate, Tribasic → HCID 89657311、化合物

HRID 632742ノート

反応式

HRID 632742 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17])[NH2:5].[CH3:18][N:19]1[CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[C:22]2[CH:34]=[CH:35][N:36]([S:37]([C:40]3[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=3)(=[O:39])=[O:38])[C:21]=2[C:20]1=[O:47].CC12CC3(C)P(C4C=CC=CC=4)C(C)(CC(C)(O3)O1)O2.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[NH2:5][C:4]1[CH:6]=[CH:7][C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])=[C:2]([C:23]2[C:22]3[CH:34]=[CH:35][N:36]([S:37]([C:40]4[CH:46]=[CH:45][C:43]([CH3:44])=[CH:42][CH:41]=4)(=[O:39])=[O:38])[C:21]=3[C:20](=[O:47])[N:19]([CH3:18])[CH:24]=2)[CH:3]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 61720969HCID 61720969、化合物HCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one

生成物 1

HCID 89657311HCID 89657311、化合物収率 72.3%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
60 °C

実験手順

A mixture of 3-bromo-4-(2,4-difluorophenoxy)aniline (5.0 g, 11.67 mmol), 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (3.85 g, 12.84 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.399 g, 1.366 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.321 g, 0.350 mmol), and potassium phosphate (6.19 g, 29.2 mmol) in dioxane (50 mL) and water (12.5 mL) was degassed and back-filled with nitrogen several times. The reaction mixture was heated at 60° C. for 16 hours and then cooled to ambient temperature. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate three times. The combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 60% ethyl acetate/hexanes) to provide 4-(5-amino-2-(2,4-difluorophenoxy)phenyl)-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one (4.40 g, 72.3% yield).

後処理

  1. customwas degassed
  2. additionback-filled with nitrogen several times
  3. temperaturecooled to ambient temperature
  4. customThe reaction mixture was partitioned between water and ethyl acetate
  5. extractionThe aqueous layer was extracted with additional ethyl acetate three times
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography (silica gel, 60% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-032ec910c4794172910ea9b145040db9
出典データセット
uspto-grants-2016_04
特許番号
US09321765B2

反応ノート

読み込み中…