4-Nitrobenzenesulfonyl chloride → HCID 15870457, compound

HRID 1355343Notes

Reaction equation

HRID 1355343 reaction equation
[Si:1]([O:18][C@@H:19]1[C@@H:23]([CH2:24]O)[O:22][C@@H:21]([N:26]2[C:43]3[N:42]=[CH:41][N:40]=[C:30]([NH:31][C:32](=[O:39])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:29]=3[N:28]=[CH:27]2)[C@@H:20]1[O:44][CH3:45])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+](C1C=CC(S(Cl)(=O)=O)=CC=1)([O-])=O.[Li][N:60]=[N+:61]=[N-:62]>>[N:60]([CH2:24][C@H:23]1[O:22][C@@H:21]([N:26]2[C:43]3[N:42]=[CH:41][N:40]=[C:30]([NH:31][C:32](=[O:39])[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:29]=3[N:28]=[CH:27]2)[C@H:20]([O:44][CH3:45])[C@@H:19]1[O:18][Si:1]([C:14]([CH3:15])([CH3:16])[CH3:17])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[N+:61]=[N-:62]

Participants

4

Reactant 3

HCID 74044-Nitrobenzenesulfonyl chlorideHCID 15405154HCID 15405154, compoundHCID 178506933HCID 178506933, compound

Product 1

HCID 15870457HCID 15870457, compound

Procedure

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).

Workup

  1. customyielded unexpectedly
  2. additiona 2:1 mixture of 5′-O-p-nitrobenzenesulfonyl and 5′-chloro-5′-deoxy substituted derivatives 14 and 15

Sources & evidence

ORD record
ord-e6a8a6595abf4ed39cb52a2d7cb6cf8d
Source dataset
uspto-grants-2003_07
Patent number
US06586238B1

Reaction notes

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