Potassium Phosphate, Tribasic → HCID 89657311, 화합물

HRID 632742노트

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HRID 632742 반응식
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

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 61720969HCID 61720969, 화합물HCID 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

생성물 1

HCID 89657311HCID 89657311, 화합물수율 72.3%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-032ec910c4794172910ea9b145040db9
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321765B2

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