Sodium Iodide → 2-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-9H-purin-6-amine

HRID 2036359Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2036359
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]([O:15][CH3:16])=[N:13][C:12]2[C:7]1=[N:8][C:9]([O:18][C@@H:19]([CH3:23])[CH2:20][CH2:21][CH3:22])=[N:10][C:11]=2[NH2:17].C(N(CC)C(C)C)(C)C.[I-].[Na+].[O:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1>C(#N)C.CS(C)=O>[CH3:23][C@H:19]([O:18][C:9]1[N:8]=[C:7]2[C:12]([N:13]=[C:14]([O:15][CH3:16])[N:6]2[CH2:5][CH2:4][CH2:3][CH2:2][NH:41][CH:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[C:11]([NH2:17])[N:10]=1)[CH2:20][CH2:21][CH3:22]

Komponenten

7

Edukt 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 4192234-AminotetrahydropyranHCID 582909339-(4-Chlorobutyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine

Produkt 1

HCID 582909342-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-9H-purin-6-amineAusbeute 36,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

9-(4-Chlorobutyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine (70 mg, 0.205 mmol) was mixed with N,N-diisopropylethylamine (0.179 ml, 1.024 mmol), sodium iodide (30.7 mg, 0.205 mmol) and tetrahydro-2H-pyran-4-amine (62.1 mg, 0.614 mmol) in acetonitrile (1.5 ml) and heated at 70° C. under nitrogen overnight and then left at ambient temperature over the weekend. The acetonitrile was evaporated under nitrogen and the residue partitioned between aqueous sodium bicarbonate and dichloromethane. The aqueous phase was re-extracted with dichloromethane and the combined organic extracts were passed through a hydrophobic frit and evaporated under nitrogen to give an amber oil. This material was dissolved in 1:1 DMSO:MeOH (2×1 ml) and purified in two injections by Mass Directed AutoPrep (Method A). Product containing fractions were combined evaporated under nitrogen in a blowdown unit to give the title compound as a colourless oil (30.35 mg).

Aufarbeitung

  1. waitleft at ambient temperature over the weekend
  2. customThe acetonitrile was evaporated under nitrogen
  3. customthe residue partitioned between aqueous sodium bicarbonate and dichloromethane
  4. extractionThe aqueous phase was re-extracted with dichloromethane
  5. customevaporated under nitrogen
  6. customto give an amber oil
  7. customMeOH (2×1 ml) and purified in two injections by Mass Directed AutoPrep (Method A)
  8. additionProduct containing fractions
  9. customwere combined evaporated under nitrogen in a blowdown unit

Quellen und Nachweise

ORD-Eintrag
ord-97ecf7c386944a34b51a83494d36858a
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08575181B2

Notizen zur Reaktion

Wird geladen…