Solution-phase synthesis of 2,6,9-trisubstituted purines

Tetrahedron Letters

Volumn 39, Issue 13, 1998, Pages 1827-1830

  Fiorini, Maria T ^a   Abell, Chris ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2,6 DICHLOROPURINE; CYCLIN DEPENDENT KINASE; ENZYME INHIBITOR; OLOMUCINE; PROTEIN KINASE; PURINE DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; CHEMICAL REACTION KINETICS; ENZYME INHIBITOR COMPLEX; ISOLATION PROCEDURE; PURINE METABOLISM; REACTION ANALYSIS; SYNTHESIS;

EID: 0032568333     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00098-7     Document Type: Article

References (17)

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11. 3N (1.1 eq) and the resulting mixture was stirred at 80 °-100 °C for 2-24 h. To isolate the product 2 the solution was allowed to cool, evaporated to dryness, taken up in ethyl acetate (5 ml), washed with water (2 × 5 ml), brine (1 × 5 ml), dried over anhydrous magnesium sulphate and concentrated in vacuo. Diethyl ether (1 ml) was added and a precipitate formed which was filtered, washed with cold water (2 ml) and cold ethanol (1 ml) and dried in vacuo. The 6-aminopurine 2 was then recrystallied from ethanol/water. This protocol can also be used for the conversion of 5 to 6.
12. 12. Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. Int. J. Pept. Prot. Res. 1991, 37, 487-493.
13. 3N (1.1 eq) at 150 °C for 30 h. Once cooled, the mixture was evaporated to dryness, taken up into DMF (5 ml) and formylpolystyrene (CHO terminating) resin (25 eq) added. The reaction was stirred at 60 °C for 24 h. The resin was then washed with DMF (3 × 3 ml) and the filtrate evaporated to dryness. The remaining mixture was evaporated to dryness, taken up in ethyl acetate, washed with water (2 × 5 ml), and brine (1 × 5 ml), dried over anhydrous magnesium sulphate and concentrated in vacuo. Diethyl ether (1 ml) was added and a precipitate formed which was filtered, washed with cold water (2 ml) and cold ethanol (1 ml) and dried in vacuo.
14. 14. Kaldor, S. W.; Seigel, M. G. Tetrahedron Lett. 1996, 37, 7193-7196.
15. 15. Benzylation of 3. Anhydrous potassium carbonate (4.6 eq) was added to a solution of the disubstituted purine (100 mg) in dry DMF (1 ml). The mixture was stirred at rt for 30 min followed by the addition of benzyl chloride (1.05 eq) The reaction was left stirring for 24 h at rt after which time the potassium carbonate was filtered off, water (10 ml) was added and a precipitate formed which was collected, washed with cold diethyl ether (5 ml) and dried in vacuo.
16. 3PO were removed by passing the mixture through a short column of silica gel using AcOEt:hexane (1:1) as eluant.
17. 3N (1.1 eq) was added tosyl chloride (1.05 eq) over 10 min. The reaction was kept at 0 °C for 2 h and left at rt for a further 24 h. The solution was then diluted with water (1 ml) and a precipitate formed which was collected by filtration, washed with cold diethyl ether and dried in vacuo.