Triethylamine → HCID 10434433, Verbindung

HRID 547257

Reaktionsgleichung

Reaktionsgleichung von HRID 547257
[OH:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:7][C:8]1[N:16]=[CH:15][N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][N:12]2[CH:17]1[C@H:21]([OH:22])[C@H:20]([OH:23])[C@@H:19]([CH2:24]Cl)[O:18]1.C(N(CC)CC)C.[H-].[Ca+2].[H-].[F:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[SH:43]>CN(C)C=O>[OH:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:7][C:8]1[N:16]=[CH:15][N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][N:12]2[CH:17]1[C@H:21]([OH:22])[C@H:20]([OH:23])[C@@H:19]([CH2:24][S:43][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[F:36])[O:18]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 5202162-FluorothiophenolHCID 3033859Calcium hydrideHCID 671894862-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]-purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diol

Produkt 1

HCID 10434433HCID 10434433, VerbindungAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]-purin-9-yl}(4S,5S,3R)-5-(chloromethyl)oxolane-3,4-diol (166.5 g, 0.457 mol) and triethylamine distilled from calcium hydride (352 ml, 256 g, 2.53 mol, 4 equivalents) in degassed anhydrous N,N-dimethylformamide (1.8 liters) was added 2-fluorothiophenol (190 ml, 228 g, 1.78 mol, 4 equiv) in 38 5 ml portions every 2-3 hours. The mixture was stirred at room temperature for 4 days with continuous bubbling of nitrogen into the solution (the reaction was monitored by 1H NMR). After the reaction was complete, the reaction mixture was poured into 7 liters of ethyl acetate, which was washed with 3 liters of water. The aqueous layer extracted with ethyl acetate (2×500 ml), and the combined organic layers were washed with water (3×2 liters), then reduced to a volume of about 1.8 liters, providing a suspension of a white solid. The suspension was stirred for 9 hours at room temperature, and the white precipitate filtered off, washed with diethyl ether (3×200 ml), and dried for 24 hours under high vacuum to give 131 g (63% yield) of 2-{6-[((1R,2R)-2-hydroxycyclopentyl)amino]purin-9-yl}(4S,5S,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol as a white powder (98.9% pure).

Aufarbeitung

  1. customwith continuous bubbling of nitrogen into the solution (the reaction
  2. additionthe reaction mixture was poured into 7 liters of ethyl acetate, which
  3. washwas washed with 3 liters of water
  4. extractionThe aqueous layer extracted with ethyl acetate (2×500 ml)
  5. washthe combined organic layers were washed with water (3×2 liters)
  6. customproviding
  7. additiona suspension of a white solid
  8. stirringThe suspension was stirred for 9 hours at room temperature
  9. filtrationthe white precipitate filtered off
  10. washwashed with diethyl ether (3×200 ml)
  11. customdried for 24 hours under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-f0d9a63915d34637af5a69b0320f85c9
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07939509B2

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