Sodium Hydroxide → HCID 78322881, Verbindung

HRID 336167

Reaktionsgleichung

Reaktionsgleichung von HRID 336167
C12BC(CCC1)CCC2.[NH2:10][C:11]1[C:12]2[C:19]([C:20]3[CH:21]=[N:22][C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][CH:24]=4)=[C:18](Br)[N:17]([CH2:31][C@@H:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH:33]=[CH2:34])[C:13]=2[N:14]=[CH:15][N:16]=1.[OH-].[Na+]>O1CCCC1>[NH2:10][C:11]1[C:12]2[C:19]([C:20]3[CH:21]=[N:22][C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][CH:24]=4)=[C:18]3[N:17]([C:13]=2[N:14]=[CH:15][N:16]=1)[CH2:31][C@@H:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:33][CH2:34]3

Komponenten

5

Edukt 3

HCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 86711295(S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate

Produkt 1

HCID 78322881HCID 78322881, VerbindungAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of 0.5 M 9-borabicyclo[3.3.1]nonane in tetrahydrofuran (141.3 ml) was added to a solution of (S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (6.0 g) obtained in Reference Example 1 in tetrahydrofuran (42 ml) under a nitrogen atmosphere at room temperature, and stirred at room temperature for 2 hours. A 2 N sodium hydroxide aqueous solution (84.8 ml) was slowly added to the reaction mixture at room temperature, and degassed under reduced pressure. Under a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (1.70 g) was added thereto, and the mixture was stirred at 66° C. for 12 hours. After the reaction mixture was cooled, the organic layer was separated and washed with a 20% ammonium chloride aqueous solution (60 ml). SH silica gel (6.0 g) was then added to the organic layer, and the result was stirred at 50° C. under a nitrogen atmosphere for 14 hours, and then filtered. SH silica gel (produced by Fuji Silysia Chemical Ltd.) (6.0 g) was added to the filtrate again, and the result was stirred under a nitrogen atmosphere at 50° C. for 14 hours, and then filtered. The solvent was distilled off from the filtrate under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain the title compound (4.46 g) (yield: 88%) as a light-yellow solid.

Aufarbeitung

  1. customdegassed under reduced pressure
  2. additionUnder a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (1.70 g) was added
  3. stirringthe mixture was stirred at 66° C. for 12 hours
  4. temperatureAfter the reaction mixture was cooled
  5. customthe organic layer was separated
  6. washwashed with a 20% ammonium chloride aqueous solution (60 ml)
  7. additionSH silica gel (6.0 g) was then added to the organic layer
  8. stirringthe result was stirred at 50° C. under a nitrogen atmosphere for 14 hours
  9. filtrationfiltered
  10. additionSH silica gel (produced by Fuji Silysia Chemical Ltd.) (6.0 g) was added to the filtrate again
  11. stirringthe result was stirred under a nitrogen atmosphere at 50° C. for 14 hours
  12. filtrationfiltered
  13. distillationThe solvent was distilled off from the filtrate under reduced pressure
  14. customThe resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-535eb036c474453f907d383ab2856978
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889666B2

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