Methanol → 1-(4-{[3-(hydroxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide

HRID 2111805Notes

Reaction equation

HRID 2111805 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][NH:8][C:9]([C:11]2[CH:34]=[CH:33][C:14]3[N:15]([C:18]4[CH:32]=[CH:31][C:21]([O:22][CH:23]5[CH2:26][CH:25]([C:27](OC)=[O:28])[CH2:24]5)=[CH:20][CH:19]=4)[CH:16]=[N:17][C:13]=3[CH:12]=2)=[O:10])[CH:2]=1.[BH4-].[Na+].CO>C1COCC1>[OH:28][CH2:27][CH:25]1[CH2:24][CH:23]([O:22][C:21]2[CH:20]=[CH:19][C:18]([N:15]3[C:14]4[CH:33]=[CH:34][C:11]([C:9]([NH:8][CH2:7][C:3]5[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=5)=[O:10])=[CH:12][C:13]=4[N:17]=[CH:16]3)=[CH:32][CH:31]=2)[CH2:26]1

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 69063376methyl 3-(4-{5-[(pyridin-3-ylmethylamino)carbonyl]-1H-benzimidazol-1-yl}phenoxy)cyclobutanecarboxylate

Product 1

HCID 690660411-(4-{[3-(hydroxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Methyl 3-(4-{5-[(pyridin-3-ylmethylamino)carbonyl]-1H-benzimidazol-1-yl}phenoxy)cyclobutanecarboxylate (150 mg, 0.33 mmol) and sodium borohydride (25 mg, 0.66 mmol) were dissolved in THF (3 mL), put under a N2 atmosphere, and heated to 60° C. Methanol (13 μL, 0.33 mmol) was then added and the reaction was stirred at 60° C. for 48 h. The reaction was cooled to rt and concentrated in vacuo. Methanol (2 mL) was then added followed by sodium hydroxide (3M, 5 mL) and the methanol was removed in vacuo. The resultant aqueous solution was extracted with ethyl acetate (3×), dried over MgSO4, filtered, and concentrated in vacuo. The crude solid was purified using the Waters mass-directed HPLC purification system to provide 1-(4-{[3-(hydroxymethyl)cyclobutyl]oxy}phenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as a white solid. MS (ES+): m/z 429 (90) [MH+].

Workup

  1. temperatureThe reaction was cooled to rt
  2. concentrationconcentrated in vacuo
  3. additionMethanol (2 mL) was then added
  4. customthe methanol was removed in vacuo
  5. extractionThe resultant aqueous solution was extracted with ethyl acetate (3×)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude solid was purified
  10. customthe Waters mass-directed HPLC purification system

Sources & evidence

ORD record
ord-26276387475942f7828855f93826f06a
Source dataset
uspto-grants-2009_04
Patent number
US07521448B2

Reaction notes

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