(S)-tert-butyl 1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethylcarbamate → (S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

HRID 2170394Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2170394
Br[C:2]1[C:3]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Cl:26][C:27]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[C:32]2[C:28]=1[C:29]([NH:46][S:47]([CH3:50])(=[O:49])=[O:48])=[N:30][N:31]2[CH3:45]>O1CCOCC1.C([O-])(O)=O.[Na+].C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[Cl:26][C:27]1[CH:35]=[CH:34][C:33]([C:2]2[C:3]([C@@H:8]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:9][C:10]3[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)=[C:32]2[C:28]=1[C:29]([NH:46][S:47]([CH3:50])(=[O:49])=[O:48])=[N:30][N:31]2[CH3:45]

Komponenten

6

Edukt 2

HCID 71185105(S)-tert-butyl 1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethylcarbamateHCID 90281256N-(4-Chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide

Produkt 1

HCID 90290217(S)-tert-butyl (1-(3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)KatalysatorHCID 312751,4-DioxaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

(S)-tert-butyl (1-(3-bromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate (1.0 g, 2.42 mmol), N-(4-chloro-1-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)methanesulfonamide (1.12 g, 2.90 mmol), and PdCl2[P(cy)3]2 (89.0 mg, 0.121 mmol) were suspended in 1,4-dioxane (108 mL) and 1.0 M aqueous NaHCO3 (36 mL). The reaction mixture was degassed by bubbling argon for 5 minutes then sealed and heated 150° C. for 15 minutes in a microwave reactor. Upon cooling, the reaction mixture was diluted with water and extracted with three portions of EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo, and purified by silica gel column chromatography, eluting with 0-100% EtOAc in hexanes to give the title compound. MS (m/z) 591.72 [M+H]+.

Aufarbeitung

  1. customThe reaction mixture was degassed
  2. customby bubbling argon for 5 minutes
  3. customthen sealed
  4. temperatureUpon cooling
  5. additionthe reaction mixture was diluted with water
  6. extractionextracted with three portions of EtOAc
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. custompurified by silica gel column chromatography
  11. washeluting with 0-100% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-4d0815ebb2234a5ba451ed03c30f71bf
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09050344B2

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