Synthesis
Example 22: Synthesis of N-[((2S,3S,4R,5R)-5-{6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-9H-purin-9-yl}-3,4-dihydroxytetrahydrofuran-2-yl)methyl]sulfonamides (1-15) Procedure a: Preparation of tert-butyloxycarbonyl aminosulfonamides; under nitrogen protection, tert-butanol (5.930 g, 0.080 mol) was dissolved in ethyl acetate (100 mL) and cooled in an acetonitrile/dry ice bath. Chlorosulfonyl isocyanate (6.964 mL, 0.080 mol) was added slowly and dropwise. The resulting clarified solution was stirred at about -40°C for 2 hours in a nitrogen atmosphere. The cooling bath was replaced with a chloroform/dry ice bath using a cold finger condenser containing acetone/dry ice placed on top of the reaction flask and ammonia was passed through to condense for 20 minutes, rapidly forming a white solid. The reaction mixture was continued to be stirred at about -60°C for 3 hours. The cold finger and cooling bath were removed and the reaction mixture was allowed to warm slowly to room temperature under a stream of nitrogen. Phase separation was performed by adding water (100 mL) and the aqueous phase was washed once with ethyl acetate (50 mL). The aqueous phase was cooled in an ice/water bath and acidified to pH~2 by dropwise addition of 20% H2SO4 aqueous solution, producing a white precipitate that was separated by filtration and washed with water. The product was dried under vacuum overnight at 40 °C to give a white solid (9.440 g, 60% yield).LCMS: retention time 1.07 min, ESI-MS m/z 195 (formic acid adduct).
References
[1] Organic Process Research and Development, 2004, vol. 8, # 3, p. 408 - 410
[2] Tetrahedron Letters, 2004, vol. 45, # 9, p. 1853 - 1856
[3] Organic Process Research and Development, 2003, vol. 7, # 5, p. 649 - 654
[4] Journal of Antibiotics, 1996, vol. 49, # 5, p. 478 - 484
[5] Angewandte Chemie, International Edition, 2009, vol. 48, p. 2777 - 2779
