4-Nitrobenzenesulfonyl chloride → HCID 15870457, compound

Participants

Reaction Steps

The low selectivity in the tosylation of guanosine derivative 6 prompted us to to use 3′-hydroxyl protection in the preparation of adenosine analog. Thus, 5′-O-DMT derivative 12 was converted to 3′-O-TBDPSi derivative which was 5′-deprotected to yield 13 with TFA in CH2Cl2. The reaction of 13 with a more reactive sulfonylating agent, p-nitrobenzenesulfonyl chloride, yielded unexpectedly a 2:1 mixture of 5′-O-p-nitrobenzenesulfonyl and 5′-chloro-5′-deoxy substituted derivatives 14 and 15. The mixture was treated with LiN3 at 80° C. overnight to afford 5′-azido-5′-deoxy derivative 16 in good yield. Catalytic hydrogenation of 16 proceeded smoothly to afford 5′-amino derivative 17 which was, without purification converted to 5′-N-MMTr protected derivative 18. Cleavage of the 3′-O-TBDPSi group was achieved using tetrabutylammonium fluoride and the resulting 19 was phosphitylated under standard conditions to give the 3′-O-phosphoramidite 20 in 74% yield (FIG. 8C).

Provenance & Evidence