Hexamethyldisilazane → 2-chloro-N6-(3-iodobenzyl)-9-[2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl]-adenine

HRID 965197Notes

Reaction equation

HRID 965197 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([I:19])[CH:14]=2)[N:3]=1.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C[Si](N[Si](C)(C)C)(C)C.CC(O[C@@H:40]1[O:44][C@H:43]([CH2:45][O:46][C:47]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:48])[C@H:42]([O:55][C:56]([C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)=[O:57])[CH:41]1[O:64][C:65]([C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[O:66])=O.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>ClC(Cl)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:40]2[O:44][C@H:43]([CH2:45][O:46][C:47](=[O:48])[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C@@H:42]([O:55][C:56](=[O:57])[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[C@H:41]2[O:64][C:65](=[O:66])[C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)=[C:4]([NH:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([I:19])[CH:14]=2)[N:3]=1

Participants

7

Reactant 5

HCID 13838HexamethyldisilazaneHCID 65367Trimethylsilyl triflateHCID 6097028Ammonium SulfateHCID 103179492-chloro-N-(3-iodobenzyl)-7H-purin-6-amineHCID 248018791-O-Acetyl-2,3,5-O-tribenzamide-D-ribose

Product 1

HCID 101019962-chloro-N6-(3-iodobenzyl)-9-[2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl]-adenineYield 91%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A mixture of 2-chloro-N6 -(3-iodobenzyl)adenine (0.84 g, 2.18 mmol), ammonium sulfate (catalytic amount), and HMDS (20 ml) was refluxed for 5 h under nitrogen to provide the silylated derivative. The clear solution was concentrated to dryness in vacuo with exclusion of moisture and the residue was dissolved in dry dichloroethane (6 ml). A solution of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranoside (Janssen Chimica Chemical Co., 1 g, 1.98 mmol) in dry dichloroethane (12 ml) and TMSOTf (0.42 ml, 2.18 mmol) was added, and the reaction mixture was stirred for 20 min at room temperature and refluxed for 14 h under nitrogen. After a workup similar to that for the compound of Example 55, the residue was purified on a silica gel column chromatography (Hx-EtOAc, 2:1) to yield 2-chloro-N6 -(3-iodobenzyl)-9-[2,3,5-tri-O-benzoyl-β-D-ribofuranosyl]-adenine [Rf =0.11 (Hx-EtOAc, 3:1), 1.495 g, 91%] as a colorless foam. 1 H NMR (CDCl3) d 4.69-4.92 (m, 5H, CH2, H-4', H-5'), 6.15 (m, 3H, H-2', H-3', NH), 6.45 (d, J=4.3 Hz, 1H, H-1'), 7.07 (pseudo t, 1H, Bn), 7.31-8.10 (m, 20H, Ar).

Workup

  1. temperaturewas refluxed for 5 h under nitrogen
  2. customto provide the silylated derivative
  3. concentrationThe clear solution was concentrated to dryness in vacuo with exclusion of moisture
  4. dissolutionthe residue was dissolved in dry dichloroethane (6 ml)
  5. temperaturerefluxed for 14 h under nitrogen
  6. customAfter a workup similar to that for the compound of Example 55, the residue was purified on a silica gel column chromatography (Hx-EtOAc, 2:1)

Sources & evidence

ORD record
ord-e008e19d3800403bb1ca5ad2877d9eb0
Source dataset
uspto-grants-1998_06
Patent number
US05773423

Reaction notes

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