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

HRID 965197노트

반응식

HRID 965197 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 63651,1-Dichloroethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e008e19d3800403bb1ca5ad2877d9eb0
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05773423

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