Toluene → propane-1-sulfonic acid {3-[1-(2,6-dichloro-benzoyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

HRID 60104

Reaktionsgleichung

Reaktionsgleichung von HRID 60104
[F:1][C:2]1[C:7]([C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([B:19]4[O:23][C:22]([CH3:25])([CH3:24])[C:21]([CH3:27])([CH3:26])[O:20]4)[CH:17]=3)[NH:12][CH:11]=2)=[O:9])=[C:6]([F:28])[CH:5]=[CH:4][C:3]=1[NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31].C1(C)C=CC=CC=1.C(NC(C)C)(C)C.[Cl:50][C:51]1[CH:59]=[CH:58][CH:57]=[C:56]([Cl:60])[C:52]=1[C:53](Cl)=[O:54]>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:50][C:51]1[CH:59]=[CH:58][CH:57]=[C:56]([Cl:60])[C:52]=1[C:53]([N:12]1[C:13]2=[N:14][CH:15]=[C:16]([B:19]3[O:20][C:21]([CH3:26])([CH3:27])[C:22]([CH3:24])([CH3:25])[O:23]3)[CH:17]=[C:18]2[C:10]([C:8]([C:7]2[C:2]([F:1])=[C:3]([NH:29][S:30]([CH2:33][CH2:34][CH3:35])(=[O:31])=[O:32])[CH:4]=[CH:5][C:6]=2[F:28])=[O:9])=[CH:11]1)=[O:54]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 7912DiisopropylamineHCID 783922,6-Dichlorobenzoyl chlorideHCID 58368878propane-1-sulfonic acid (2,4-difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl)-amide

Produkt 1

HCID 58368752propane-1-sulfonic acid {3-[1-(2,6-dichloro-benzoyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Propane-1-sulfonic acid {2,4-difluoro-3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide (30, 2.1 g, 4.16 mmol), 21 mL of toluene, diisopropylamine (1.5 mL, 8.31 mmol), 4-dimethylaminopyridine (101 mg, 0.83 mmol) and 2,6-dichloro-benzoyl chloride (10, 0.7 mL, 4.78 mmol) are combined in a reaction flask under nitrogen. The reaction is stirred at room temperature for 17 hours, then diluted with 100 mL of ethyl acetate and extracted. The organic layer is washed sequentially with 40 mL of saturated aqueous sodium bicarbonate, 40 mL of water, and 40 mL of brine, then dried with sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with a gradient of ethyl acetate and hexane. Appropriate fractions are combined and concentrated under vacuum and the resulting material is triturated with diethyl ether to provide the desired compound.

Aufarbeitung

  1. extractionextracted
  2. washThe organic layer is washed sequentially with 40 mL of saturated aqueous sodium bicarbonate, 40 mL of water, and 40 mL of brine
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under vacuum
  6. customThe resulting material is purified by silica gel column chromatography
  7. washeluting with a gradient of ethyl acetate and hexane
  8. concentrationconcentrated under vacuum
  9. customthe resulting material is triturated with diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-6bbb0535581a4d15b116704b9443d3c9
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440969B2

Verknüpfte Notizen

Wird geladen…