Trimethylsilyl triflate → 5,6-Dichloro-7-fluoro-1-(2,3-di-o-acetyl-5-deoxy-beta-d-ribofuranosyl)-n-(1-methylethyl)-1h-benzimidazol-2-amine

HRID 2227190Notes

Reaction equation

HRID 2227190 reaction equation
[Cl:1][C:2]1[C:14]([Cl:15])=[CH:13][C:5]2[NH:6][C:7]([NH:9][CH:10]([CH3:12])[CH3:11])=[N:8][C:4]=2[C:3]=1[F:16].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(O[CH:45]1[O:57][C@H:56]([CH3:58])[C@@H:51]([O:52][C:53](=[O:55])[CH3:54])[C@H:46]1[O:47][C:48](=[O:50])[CH3:49])(=O)C>ClCCCl>[Cl:15][C:14]1[C:2]([Cl:1])=[C:3]([F:16])[C:4]2[N:8]([C@@H:45]3[O:57][C@H:56]([CH3:58])[C@@H:51]([O:52][C:53](=[O:55])[CH3:54])[C@H:46]3[O:47][C:48](=[O:50])[CH3:49])[C:7]([NH:9][CH:10]([CH3:12])[CH3:11])=[N:6][C:5]=2[CH:13]=1

Participants

6

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 11196237Tri-O-acetyl-5-deoxy-D-ribofuranoseHCID 184721125,6-Dichloro-4-fluoro-N-(1-methylethyl)-1H-benzimidazol-2-amine

Product 1

HCID 538148955,6-Dichloro-7-fluoro-1-(2,3-di-o-acetyl-5-deoxy-beta-d-ribofuranosyl)-n-(1-methylethyl)-1h-benzimidazol-2-amineYield 26%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

5,6-Dichloro-4-fluoro-N-(1-methylethyl)-1H-benzimidazol-2-amine (0.85 g, 3.24 mmol), N,O-bis(trimethylsilyl)acetamide (0.89 mL, 0.73 g, 3.60 mmol), trimethylsilyl trifluromethanesulfonate (0.45 mL, 0.53 g, 2.25 mmol), 1,2,3-tri-O-acetyl-5-deoxy-ribofuranose (1.15 g, 4.42 mmol) and 1,2-dichloroethane were used according to general procedure II. The title compounds were purified by silica gel chromatography using 95:5 dichloromethane-acetonitrile to first provide 5,6-dichloro-4-fluoro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine as a white foam (0.66 g, 44%); 1H NMR (DMSO-d6) δ: 7.49 (s, 1H, Ar—H), 7.05 (d, J=7.4 Hz, 1H, NH), 6.09 (d, J=6.8 Hz, 1H, CH), 5.57 (t, J=7.2 Hz, 1H, CH), 5.24 (dd, J=7.4, 5.3 Hz, 1H, CH), 4.12 (m, 2H, overlapping CH), 2.14 (s, 3H, CH3), 2.01 (s, 3H, CH3), 1.49 (d, J=6.3 Hz, CH3), 1.24 (m, 6H, overlapping CH3). The second fraction provided 5,6-dichloro-7-fluoro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine as a white foam (0.39 g, 26%); 1H NMR (DMSO-d6) δ: 7.37 (s, 1H, Ar—H), 7.12 (d, J=7.4 Hz, 1H, NH), 6.08 (d, J=5.4 Hz, 1H, CH), 5.32 (t, J=6.8 Hz, 1H, CH), 4.98 (t, J=7.3 Hz, 1H, CH), 4.10 (m, 2H, overlapping CH), 2.10 (s, 3H, CH3), 2.04 (s, 3H, CH3), 1.41 (d, J=6.2 Hz, CH3), 1.23 (m, 6H, overlapping CH3).

Workup

  1. customThe title compounds were purified by silica gel chromatography

Sources & evidence

ORD record
ord-b0bcc5b73e0147b492aa820b9f9488a3
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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