Sodium Hydroxide → HCID 10450477, compound

HRID 31490Notes

Reaction equation

HRID 31490 reaction equation
N[CH2:2][C:3]1[O:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[C:16]([C:21]([NH:23][CH:24]4[CH2:26][CH2:25]4)=[O:22])[CH:15]=3)=[CH:10][CH:9]=2)=[N:5][N:4]=1.N([O-])=[O:28].[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH:24]1([NH:23][C:21]([C:16]2[CH:15]=[C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:6]4[O:7][C:3]([CH2:2][OH:28])=[N:4][N:5]=4)=[CH:9][CH:10]=3)[C:19]([CH3:20])=[CH:18][CH:17]=2)=[O:22])[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 99978914'-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1'-biphenyl-3-carboxamideHCID 23668193Sodium Nitrite

Product 1

HCID 10450477HCID 10450477, compound

Reagents, catalysts & solvents 1

HCID 21899381Acetic acid--water (1/1)Solvent

Procedure

A solution of 4′-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1′-biphenyl-3-carboxamide (Example 53) (30 mg) in acetic acid/water (1:1 v/v, 3 ml) was cooled to 0° C. Sodium nitrite (68 mg) was added and the solution stirred 24 hours at room temperature. Concentrated sodium hydroxide solution was added to the reaction and the mixture extracted with ether (3×20 ml). The combined organic phases were treated with potassium hydroxide in methanol (5%, 3 ml) for 2 hours, washed with water, dried (sodium sulphate) and reduced to dryness under vacuum. The residue was dissolved in 5% potassium hydroxide in methanol and stirred at room temperature for 90 minutes. The methanol was removed in vacuo, the residue partitioned between ethyl acetate/chloroform (1:1)/water and the organic phase dried and reduced to dryness under vacuum. This material was purified by HPLC, to give, after evaporation of the solvent, N-cyclopropyl-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide.

Workup

  1. extractionthe mixture extracted with ether (3×20 ml)
  2. additionThe combined organic phases were treated with potassium hydroxide in methanol (5%, 3 ml) for 2 hours
  3. washwashed with water
  4. dry with materialdried (sodium sulphate)
  5. dissolutionThe residue was dissolved in 5% potassium hydroxide in methanol
  6. stirringstirred at room temperature for 90 minutes
  7. customThe methanol was removed in vacuo
  8. customthe residue partitioned between ethyl acetate/chloroform (1:1)/water
  9. customthe organic phase dried
  10. customThis material was purified by HPLC
  11. customto give
  12. customafter evaporation of the solvent, N-cyclopropyl-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide

Sources & evidence

ORD record
ord-2db587f2fbf54ba79a981823fa955917
Source dataset
uspto-grants-2008_09
Patent number
US07425555B2

Reaction notes

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