Water → 2-[3-(4-benzyloxybutoxy)-4-(3-methanesulfonylphenyl)benzylamino]-1-(beta-D-ribofuranosyl)-1H-benzimidazole

HRID 1985854Notes

Reaction equation

HRID 1985854 reaction equation
[NH2:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][O:21]C(=O)C)[C@@H:13]([O:14]C(=O)C)[C@H:8]2[O:9]C(=O)C)[C:5]2[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=2[N:3]=1.[CH2:29]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][C:49]=1[C:50]1[CH:55]=[CH:54][CH:53]=[C:52]([S:56]([CH3:59])(=[O:58])=[O:57])[CH:51]=1)[CH:45]=O)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>O1CCCC1>[CH2:29]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][C:49]=1[C:50]1[CH:55]=[CH:54][CH:53]=[C:52]([S:56]([CH3:59])(=[O:58])=[O:57])[CH:51]=1)[CH2:45][NH:1][C:2]1[N:6]([C@@H:7]2[O:19][C@H:18]([CH2:20][OH:21])[C@@H:13]([OH:14])[C@H:8]2[OH:9])[C:5]2[CH:25]=[CH:26][CH:27]=[CH:28][C:4]=2[N:3]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 231438543-(4-Benzyloxybutoxy)-4-(3-methanesulfonylphenyl)benzaldehydeHCID 688410382-Amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1H-benzimidazole

Product 1

HCID 688440572-[3-(4-benzyloxybutoxy)-4-(3-methanesulfonylphenyl)benzylamino]-1-(beta-D-ribofuranosyl)-1H-benzimidazoleYield 82.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-benzimidazole (0.11 g) and 3-(4-benzyloxybutoxy)-4-(3-methanesulfonylphenyl)benzaldehyde (0.24 g) were suspended in tetrahydrofuran (5 mL). To the reaction mixture was added sodium triacetoxyborohydride (0.12 g), and the mixture was stirred at room temperature for 24 hours. After adding water to the reaction mixture, the mixture was concentrated under reduced pressure. The obtained residue was dissolved in methanol (2 mL). To the mixture was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added acetic acid (1 mL), and the mixture was concentrated under reduced pressure. The obtained residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELL PAC C18UG80, 5 μm, 20×50 mm, flow rate 30 mL/minutes linear gradient, water/methanol=70/30-10/90) to give 2-[3-(4-benzyloxybutoxy)-4-(3-methanesulfonylphenyl)benzylamino]-1-(β-D-ribofuranosyl)-1H-benzimidazole (0.16 g). The obtained compound was dissolved in methanol (2 mL). To the solution was added a catalytic amount of 10% palladium-carbon powder, and the mixture was stirred at 40° C. under a hydrogen atmosphere for 24 hour. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (0.04 g).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. dissolutionThe obtained residue was dissolved in methanol (2 mL)
  3. additionTo the mixture was added 5 mol/L aqueous sodium hydroxide solution (0.5 mL)
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. additionTo the reaction mixture was added acetic acid (1 mL)
  6. concentrationthe mixture was concentrated under reduced pressure
  7. customThe obtained residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELL PAC C18UG80, 5 μm, 20×50 mm, flow rate 30 mL/minutes linear gradient, water/methanol=70/30-10/90)

Sources & evidence

ORD record
ord-c5cf471551dc4ad6810734210b9bd4e6
Source dataset
uspto-grants-2009_06
Patent number
US07547680B2

Reaction notes

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