Potassium Phosphate, Tribasic → N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide

HRID 632746노트

반응식

HRID 632746 반응식
[CH3:1][N:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3]1=[O:30].Br[C:32]1[CH:33]=[C:34]([NH:47][S:48]([CH2:51][CH3:52])(=[O:50])=[O:49])[CH:35]=[CH:36][C:37]=1[O:38][C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=1[F:46].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].CC12CC3(C)P(C4C=CC=CC=4)C(C)(CC(C)(O3)O1)O2>[F:46][C:40]1[CH:41]=[C:42]([F:45])[CH:43]=[CH:44][C:39]=1[O:38][C:37]1[CH:32]=[CH:33][C:34]([NH:47][S:48]([CH2:51][CH3:52])(=[O:49])=[O:50])=[CH:35][C:36]=1[C:6]1[C:5]2[CH:17]=[CH:18][N:19]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:4]=2[C:3](=[O:30])[N:2]([CH3:1])[CH:7]=1

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 867210626-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-oneHCID 117770988N-(3-bromo-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide

생성물 1

HCID 117773894N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide수율 93.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane촉매

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온도
60 °C

실험 절차

A mixture of 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 (6.00 g, 14.0 mmol), N-(3-bromo-4-(2,4-difluorophenoxy)phenyl)ethanesulfonamide (5.77 g, 14.7 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.205 g, 0.700 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.321 g, 0.350 mmol) and potassium phosphate (2.97 g, 14.0 mmol) was combined and sparged with argon for 30 minutes. A mixture of dioxane (60 mL) and water (15 mL) was sparged with nitrogen for 30 minutes and transferred by syringe into the reaction vessel under argon. The reaction mixture was stirred at 60° C. for 2 hours, cooled to ambient temperature, and partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (anhydrous sodium sulfate), treated with silica gel (2-4 g) for 45 minutes, filtered and concentrated to afford N-(4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1-tosyl-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl)ethanesulfonamide (8 g, 13.04 mmol, 93% yield).

후처리

  1. customsparged with argon for 30 minutes
  2. additionA mixture of dioxane (60 mL) and water (15 mL)
  3. customwas sparged with nitrogen for 30 minutes
  4. customtransferred by syringe into the reaction vessel under argon
  5. temperaturecooled to ambient temperature
  6. custompartitioned between ethyl acetate and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried (anhydrous sodium sulfate)
  9. additiontreated with silica gel (2-4 g) for 45 minutes
  10. filtrationfiltered
  11. concentrationconcentrated

출처 및 근거

ORD 기록
ord-99fabf65b0754003af0efabd2db932f5
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321765B2

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