1,2-Dimethoxyethane → 2-(Cyclobutyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 527811

Reaktionsgleichung

Reaktionsgleichung von HRID 527811
CC(C)([O-])C.[Na+].[CH:7]1([OH:11])[CH2:10][CH2:9][CH2:8]1.F[C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[C:15]([NH2:28])[N:14]=1.COCCOC>ClCCl>[CH:7]1([O:11][C:13]2[N:21]=[C:20]3[C:16]([N:17]=[CH:18][N:19]3[CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][O:23]3)=[C:15]([NH2:28])[N:14]=2)[CH2:10][CH2:9][CH2:8]1

Komponenten

6

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 76218CyclobutanolHCID 23676156Sodium t-butoxideHCID 592525662-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Produkt 1

HCID 592526272-(Cyclobutyloxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Sodium t-butoxide (3.31 g, 34.2 mmol) was added portionwise to cyclobutanol (10 ml) at room temperature. The mixture became very thick and was heated to 50° C. 2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (2 g, 8.43 mmol) was added followed by 1,2-dimethoxyethane (3 ml) and the mixture stirred at 50° C. for 90 mins. and then cooled and partitioned between ethyl acetate (50 ml) and water (50 ml). A precipitate that failed to dissolve in either phase was removed by filtration. The organic phase was separated, washed with saturated brine, dried over anhydrous magnesium sulphate, filtered and evaporated to give a cream foam. This material was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (110 g) using a 0-100% ethyl acetate in cyclohexane gradient followed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (0.655 g).

Aufarbeitung

  1. temperatureand then cooled
  2. custompartitioned between ethyl acetate (50 ml) and water (50 ml)
  3. dissolutionto dissolve in either phase
  4. customwas removed by filtration
  5. customThe organic phase was separated
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customto give a cream foam
  11. custompurified on an aminopropyl (NH2) cartridge (110 g)
  12. waitfollowed by a 0-20% methanol (+1% triethylamine) gradient over 40 mins
  13. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-068379d7a6284a46baec3a33b235b521
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09346806B2

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