Ammonia → 5-[6-(Hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide

HRID 2391576Notes

Reaction equation

HRID 2391576 reaction equation
[Si]([O:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24](OC)=[O:25])=[C:21]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[C:36]([F:39])([F:38])[F:37])[CH:20]=3)[C:12]=2[CH:11]=1)(C(C)(C)C)(C)C.[NH3:40]>CO>[OH:8][CH2:9][C:10]1[N:15]=[CH:14][C:13]2[N:16]=[CH:17][N:18]([C:19]3[S:23][C:22]([C:24]([NH2:40])=[O:25])=[C:21]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[C:36]([F:38])([F:37])[F:39])[CH:20]=3)[C:12]=2[CH:11]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 68766097Methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate

Product 1

HCID 251528665-[6-(Hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3.15 g of methyl 5-[6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1H-imidazo[4,5-c]pyridin-1-yl]-3-{[2-(trifluoromethyl)benzyl]oxy}thiophene-2-carboxylate (compound B2b) and 218 ml of a saturated solution of ammonia in methanol was stirred in an autoclave at 120° C. for 3 h. The mixture was allowed to cool down to room temperature and concentrated to dryness to give the crude corresponding acid amide that was immediately used for the next step without further purification. The residue was dissolved in 180 ml tetrahydrofuran and to this solution is added 2.0 ml of tetra-n-butylammonium fluoride solution (˜75% in H2O) at 0° C. The reaction mixture was stirred at 0° C. for 12 h. The solvent was evaporated and the residue was treated with 250 ml dichloromethane and 60 ml saturated aqueous NaHCO3 solution. The resulting precipitate was dissolved by addition of propan-2-ol, the organic layer was separated, washed with 60 ml saturated aqueous NaHCO3 solution, dried with MgSO4 and concentrated under vacuum. The residue was suspended in 40 ml dichloromethane and stirred for one hour. The suspension was filtered, the filter cake washed with 20 ml dichloromethane and dried under vacuum to yield the title compound.

Workup

  1. temperatureto cool down to room temperature
  2. concentrationconcentrated to dryness
  3. customto give the crude corresponding acid amide that
  4. customwas immediately used for the next step without further purification
  5. dissolutionThe residue was dissolved in 180 ml tetrahydrofuran and to this solution
  6. additionis added 2.0 ml of tetra-n-butylammonium fluoride solution (˜75% in H2O) at 0° C
  7. stirringThe reaction mixture was stirred at 0° C. for 12 h
  8. customThe solvent was evaporated
  9. additionthe residue was treated with 250 ml dichloromethane and 60 ml saturated aqueous NaHCO3 solution
  10. dissolutionThe resulting precipitate was dissolved by addition of propan-2-ol
  11. customthe organic layer was separated
  12. washwashed with 60 ml saturated aqueous NaHCO3 solution
  13. dry with materialdried with MgSO4
  14. concentrationconcentrated under vacuum
  15. stirringstirred for one hour
  16. filtrationThe suspension was filtered
  17. washthe filter cake washed with 20 ml dichloromethane
  18. customdried under vacuum

Sources & evidence

ORD record
ord-55217c0b52bf4c888743bb7884f71536
Source dataset
uspto-grants-2012_09
Patent number
US08273890B2

Reaction notes

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