Reaktion #1782268

Reaktionsgleichung

trifluoroacetic acid

NaH

2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide

N9-(3-Azidopropyl)-2-amino-6-chloropurine

N9-(3-Azidopropyl)-2-amino-6-chlorpurine

→

N-[4-(2-Amino-9-(3-azidopropyl)-purine-6-yloxymethyl)-benzyl]-2,2,2-trifluoro-acetamide

Lösungsmittel

water

dimethylacetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   ExtraktionThe aqueous phase is extracted with CH2Cl2 and ethyl acetate
3. 3
   WaschenThe organic phases are washed with water and brine
4. 4
   Trocknendried over MgSO4
5. 5
   Sonstigethe solvent is evaporated
6. 6
   workup.DISSOLUTIONThe crude product is dissolved in methanol
7. 7
   Sonstigepurified by flash column chromatography with dichloromethane:methanol (95:5)

Vorschrift

2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide (138 mg, 0.59 mmol) is dissolved in 3 mL dry dimethylacetamide under argon atmosphere, and (31 mg, 1.31 mmol) NaH is added. N9-(3-Azidopropyl)-2-amino-6-chloropurine (22, 100 mg, 0.39 mmol) is added and the solution heated to 90° C. for 16 h. After cooling to room temperature, the mixture is poured into 80 mL of water and the pH is adjusted to 6 with trifluoroacetic acid. The aqueous phase is extracted with CH2Cl2 and ethyl acetate. The organic phases are washed with water and brine, dried over MgSO4 and the solvent is evaporated. The crude product is dissolved in methanol, adsorbed on SiO2 (150 mg) and purified by flash column chromatography with dichloromethane:methanol (95:5). Yield: 151 mg (0.0336 mmol, 85%). 1H-NMR (400 MHz, DMSO-d6): δ=10.00 (t, J=5.8, 1H, CF3CONH), 7.90 (s, 1H, H-8), 7.49, (d, J=8.1, 2H, ArH), 7.28 (d, J=8.1, 2H, ArH), 6.47 (s br, 2H, NH2), 5.46 (s, 2H, OCH2), 4.38 (d, J=5.8, 2H, CH2NH), 4.06 (t, J=6.5, 2H, CH2), 3.36 (t, J=6.5, 2H, CH2), 2.00 (m, 2H, CH2) ppm. MS (ESI) m/z 450.0 [M+H]+.

Quelle