N,N-Diethylaniline → (R)-2-Amino-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)-6-chloropurine

HRID 48556

Reaktionsgleichung

Reaktionsgleichung von HRID 48556
[C:1]([O:20][CH2:21][C@H:22]([CH2:35][CH2:36][O:37][C:38](=[O:51])[C@H:39]([CH:48]([CH3:50])[CH3:49])[NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:23][N:24]1[CH:32]=[N:31][C:30]2[C:29](=O)[NH:28][C:27]([NH2:34])=[N:26][C:25]1=2)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:65])=O>C(#N)C.[Cl-].C[N+](C)(C)C>[NH2:34][C:27]1[N:26]=[C:25]2[C:30]([N:31]=[CH:32][N:24]2[CH2:23][C@H:22]([CH2:21][O:20][C:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:35][CH2:36][O:37][C:38](=[O:51])[C@H:39]([CH:48]([CH3:50])[CH3:49])[NH:40][C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])=[C:29]([Cl:65])[N:28]=1

Komponenten

6

Edukt 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 135796494(R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine

Produkt 1

HCID 53751265(R)-2-Amino-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)-6-chloropurine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6379Tetramethylammonium chlorideKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (R)-9-(2-stearoyloxymethyl-4-(N-tert-butoxycarbonyl-L-valyloxy)butyl)guanine from step 2 of Example 1 (646 mg, 0.9 mmole) in acetonitrile were added tetramethylammonium chloride (427 mg, 2.7 mmole), N,N-diethylaniline (0.716 ml, 4.5 mmole) and phosphorous oxychloride (0.417 ml, 4.5 mmole). The reaction was kept under reflux and the progression monitored by TLC. After 3 hours the reaction mixture was evaporated in vacuo and the residue was dissolved in dichloromethane, then poured into cold sodium hydrogen carbonate aqueous solution. The organic phase was evaporated and purified by silica gel column chromatography. Yield: 251 mg.

Aufarbeitung

  1. temperatureunder reflux
  2. customAfter 3 hours the reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in dichloromethane
  4. additionpoured into cold sodium hydrogen carbonate aqueous solution
  5. customThe organic phase was evaporated
  6. custompurified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-f89c35cd0b20477090c85eea32b0ce0d
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06703394B2

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