4-Methylmorpholine → Ethyl 9-{(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-[(acetyloxy)methyl]tetrahydro-2-furanyl}-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate

HRID 10467

Reaktionsgleichung

Reaktionsgleichung von HRID 10467
[C:1]1([CH:7]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(O[C@@H:53]1[O:65][C@H:64]([CH2:66][O:67][C:68](=[O:70])[CH3:69])[C@@H:59]([O:60][C:61](=[O:63])[CH3:62])[C@H:54]1[O:55][C:56](=[O:58])[CH3:57])(=O)C.C(=O)(O)[O-].[Na+]>COCCOC.C(OCC)(=O)C>[C:56]([O:55][C@@H:54]1[C@H:59]([O:60][C:61](=[O:63])[CH3:62])[C@@H:64]([CH2:66][O:67][C:68](=[O:70])[CH3:69])[O:65][C@H:53]1[N:14]1[CH:13]=[N:12][C:11]2[C:15]1=[N:16][C:17]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[N:18][C:10]=2[NH:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:58])[CH3:57]

Komponenten

8

Edukt 5

HCID 79724-MethylmorpholineHCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 516892Sodium BicarbonateHCID 178419102HCID 178419102, Verbindung

Produkt 1

HCID 10122270Ethyl 9-{(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-[(acetyloxy)methyl]tetrahydro-2-furanyl}-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 80711,2-DimethoxyethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

To a suspension of ethyl 6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate (Preparation 63) (40.0 g, 0.103 moles) in anhydrous 1,2-dimethoxyethane (240 ml) under an atmosphere of nitrogen was added 4-methylmorpholine (11.5 g, 12.5 ml, 0.114 moles) and the resultant mixture was heated to 45° C. with stirring. To this mixture was then added trimethylsilyl trifluoromethanesulphonate (27.5 g, 22.4 ml, 0.124 moles) over a period of 10 minutes. The resultant orange solution was then heated to 55° C., and a solution of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose (36.1 g, 0.113 moles) in 1,2-dimethoxyethane (100 ml plus 20 ml to rinse through) was added over a period of 10 minutes. The reaction was then stirred at 57–60° C. for 2 hours after which time the mixture was cooled to ambient temperature. The reaction mixture was then cautiously added to a mixture of saturated aqueous sodium bicarbonate solution (400 ml) and ethyl acetate (400 ml) with vigorous stirring. The layers were separated and the aqueous phase was extracted with ethyl acetate (400 ml). The combined organic phases were dried over anhydrous magnesium sulphate and were then concentrated in vacuo to give the crude product as an orange foam (74.9 g) that could be used as such for the next step. This crude product can be purified using flash chromatography on silica gel eluting with a gradient system of 10% v/v diethyl ether in dichloromethane changing to 25% v/v diethyl ether in dichloromethane to give the title compound as a colourless foam.

Aufarbeitung

  1. stirringThe reaction was then stirred at 57–60° C. for 2 hours after which time the mixture
  2. temperaturewas cooled to ambient temperature
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with ethyl acetate (400 ml)
  5. dry with materialThe combined organic phases were dried over anhydrous magnesium sulphate
  6. concentrationwere then concentrated in vacuo
  7. customto give the crude product as an orange foam (74.9 g) that
  8. customThis crude product can be purified

Quellen und Nachweise

ORD-Eintrag
ord-24077634027d402792edb18726eda7e5
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07094769B2

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