Tetrahydrofuran → Cyclopentyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amine

HRID 459956Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 459956
[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[N:13]=[CH:14][C:15]1[C:16]([NH:23][CH2:24][CH3:25])=[N:17][C:18]([S:21][CH3:22])=[N:19][CH:20]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O1C[CH2:35][CH2:34][CH2:33]1>>[CH:24]1([NH:23][C:16]2[C:15]([CH2:14][NH:13][C:3]3[C:4]([F:12])=[C:5]([O:10][CH3:11])[CH:6]=[C:7]([O:8][CH3:9])[C:2]=3[F:1])=[CH:20][N:19]=[C:18]([S:21][CH3:22])[N:17]=2)[CH2:35][CH2:34][CH2:33][CH2:25]1

Komponenten

4

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 18444815(5-[(2,6-Difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-ethyl-amineHCID 21226445Aluminium lithium hydride

Produkt 1

HCID 18444835Cyclopentyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylamino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amineAusbeute 76 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 25.30 g (assume 0.0523 mol) of (5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-ethyl-amine in 425 mL of anhydrous tetrahydrofuran was cooled to 0° C. using an ice/acetone bath. The cooled mixture was treated dropwise via syringe with 78.50 mL (0.0785 mol) 1 M solution of lithium aluminum hydride in tetrahydrofuran which resulted initially with vigorous bubbling. The resulting mixture continued to stir at 0° C. for 1 hour under nitrogen atmosphere. The ice bath was removed and the reaction mixture was allowed to warm up to room temperature and continued stirring at room temperature overnight. The reaction mixture was cooled to 0° C. using an ice/acetone bath and quenched by the slow addition of 78.50 mL of water, 78.50 mL of 15% sodium hydroxide and 157 mL of water. The salts were filtered over a bed of Celite and removed the tetrahydrofuran in vacuo. The residue was redissolved in dichloromethane and filtered again. The layers were separated and dried the organic layer over sodium sulfate, filtered and evaporated. The crude product was purified using medium-pressure chromatography eluting with a gradient of 2:1 to 1:1 hexanes/ethyl acetate to give 16.34 g (76%) of title compound. MS (APCI) (m+1)/z 411.1.

Aufarbeitung

  1. customresulted initially with vigorous bubbling
  2. customThe ice bath was removed
  3. temperatureto warm up to room temperature
  4. stirringcontinued stirring at room temperature overnight
  5. temperatureThe reaction mixture was cooled to 0° C.
  6. customquenched by the slow addition of 78.50 mL of water, 78.50 mL of 15% sodium hydroxide and 157 mL of water
  7. filtrationThe salts were filtered over a bed of Celite
  8. customremoved the tetrahydrofuran in vacuo
  9. dissolutionThe residue was redissolved in dichloromethane
  10. filtrationfiltered again
  11. customThe layers were separated
  12. dry with materialdried the organic layer over sodium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customThe crude product was purified
  16. washeluting with a gradient of 2:1 to 1:1 hexanes/ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-e1fa3b7e62c54519a6bbbf1bacda78b0
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07196090B2

Notizen zur Reaktion

Wird geladen…