反应详情

温度

80 °C

A mixture of 2-amino-6-chloropurine (Aldrich Chemical Co.) 11.2 g, 0.066 mol) hexamethyldisilazane (160 ml), and ammonium sulfate (1.09 g) is refluxed for 2.5 hours and then cooled, concentrated and pumped to dryness. The residue is dissolved in dry toluene (210 ml) and is treated with Hg(CN)2. The mixture is heated to 80° C. and a solution of 2-(chloromethoxy)-1-(heptyloxy-3-(phenylmethoxy) propane (prepared from 1-(heptyloxy)-3-(phenylmethoxy)-2-propanol (19 g, 0.068 mol), paraformaldehyde (4 g) and dry HCl (g) in CH2Cl2 (160 ml) as described in the first part of Example 7, in toluene (210 ml) is added to the solution and heated to 80°-85° C. for 2.5 hours. The mixture is cooled, concentrated, and diluted with CH2Cl2 (1.0 L) and is allowed to stand overnight. The CH2Cl2 solution is filtered, washed with 30% KI, 10% potassium carbonate solution and water. The organic layer is dried and concentrated. The residue is chromatographed over silica gel column using a high pressure liquid chromatographic instrument (Waters Prep 500). The column is eluted with ethyl acetate and hexane (1:1) to give the condensation product (i.e., chloropurine derivative) (6.45 g) which is hydrolysed as follows.

1. temperatureis refluxed for 2.5 hours
2. temperaturecooled
3. concentrationconcentrated
4. dissolutionThe residue is dissolved in dry toluene (210 ml)
5. additionis treated with Hg(CN)2
6. additionis added to the solution
7. temperatureheated to 80°-85° C. for 2.5 hours
8. temperatureThe mixture is cooled
9. concentrationconcentrated
10. additiondiluted with CH2Cl2 (1.0 L)
11. filtrationThe CH2Cl2 solution is filtered
12. washwashed with 30% KI, 10% potassium carbonate solution and water
13. customThe organic layer is dried
14. concentrationconcentrated
15. customThe residue is chromatographed over silica gel column
16. washThe column is eluted with ethyl acetate and hexane (1:1)