Lithium Hydroxide → 4,5-Dichloro-1-(5deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine

HRID 2227179Notes

Reaction equation

HRID 2227179 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][CH:12]([CH3:14])[CH3:13])[N:7]([C@@H:15]3[O:27][C@H:26]([CH3:28])[C@@H:21]([O:22]C(=O)C)[C@H:16]3[O:17]C(=O)C)[C:6]=2[CH:5]=[CH:4][C:3]=1[Cl:29].[OH-].[Li+]>O1CCOCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][CH:12]([CH3:14])[CH3:13])[N:7]([C@@H:15]3[O:27][C@H:26]([CH3:28])[C@@H:21]([OH:22])[C@H:16]3[OH:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[Cl:29]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 570527734,5-Dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine

Product 1

HCID 220862714,5-Dichloro-1-(5deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amineYield 72.2%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

4,5-Dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine (0.82 g, 1.8 mmol) was dissolved in 1,4dioxane (Aldrich, 20 mL). Aqueous lithium hydroxide (5.5 mL, 1.0 M, 5.5 mmol) was added and the mixture was stirred for 30 min. The solution was then diluted with brine (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were dried over magnesium sulfate, filtered, and evaporated. The crude residue was purified on a silica gel column (5×20 cm, 230-400 mesh) with 96:4 dichloromethane-methanol to give the title compound (0.48 g, 1.3 mmol, 72%); MS (AP+): m/z 360 (M+1); 1H NMR (DMSO-d6) δ: 7.11 (d, 1H, Ar—H, J=8.7 Hz), 7.04 (d, 1H, Ar—H, J=8.4 Hz), 6.75 (d, 1H, NH, J=7.5 Hz), 5.70 (d, 1H, H-1′, J=6.3 Hz), 5.27 (d, 1H, OH, J=6.6 Hz), 5.22 (d, 1H, OH, J=4.8 Hz), 4.28-4.35 (m, 1H, CH), 4.05-4.16 (m, 1H, CH), 3.77-3.92 (m, 2H, CH), 1.35 (d, 3H, 5′-CH3, J=6.6 Hz), 1.22 (d, 6H, CH3, J=6.6 Hz).

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. dry with materialThe organic layers were dried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude residue was purified on a silica gel column (5×20 cm, 230-400 mesh) with 96:4 dichloromethane-methanol

Sources & evidence

ORD record
ord-f50863d2f9b8420daea85460b4f278c7
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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