Sodium Hydroxide → N-Cyclopropyl-5-fluoro-4'-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1'-biphenyl-3-carboxamide

HRID 31471

반응식

HRID 31471 반응식
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])=[C:18]([F:21])[CH:17]=[C:16]([C:22]([NH:24][CH:25]4[CH2:27][CH2:26]4)=[O:23])[CH:15]=3)=[CH:10][CH:9]=2)=[N:5][N:4]=1.N([O-])=[O:29].[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH:25]1([NH:24][C:22]([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:29])=[N:4][N:5]=4)=[CH:9][CH:10]=3)[C:19]([CH3:20])=[C:18]([F:21])[CH:17]=2)=[O:23])[CH2:26][CH2:27]1

참가 물질

5

반응물 3

HCID 14798Sodium HydroxideHCID 104289704'-[5-(aminomethyl)-1,3,4oxadiazol-2-yl]-N-cyclopropyl-5-fluoro-6-methyl-1,1'-biphenyl-3-carboxamideHCID 23668193Sodium Nitrite

생성물 1

HCID 9976225N-Cyclopropyl-5-fluoro-4'-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1'-biphenyl-3-carboxamide

시약·촉매·용매 1

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

반응 조건

온도
0 °C

실험 절차

A solution of 4′-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-5-fluoro-6-methyl-1,1′-biphenyl-3-carboxamide (Example 45) (96 mg) in acetic acid/water (1:1 v/v, 7 ml) was cooled to 0° C. Sodium nitrite (206 mg) was added and the solution stirred for 30 minutes at 0° C. and then for a further 16 hours at room temperature. Concentrated sodium hydroxide solution (10 ml) was added to the reaction and the mixture extracted with ether (3×40 ml) and then chloroform (40 ml). The organic phases were combined, dried 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 chromatography on a bond-elut (silica, 2 g), eluting with an ethyl acetate/cyclohexane gradient to give after evaporation of the solvent N-cyclopropyl-5-fluoro-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide.

후처리

  1. waitfor a further 16 hours at room temperature
  2. extractionthe mixture extracted with ether (3×40 ml)
  3. customdried
  4. dissolutionThe residue was dissolved in 5% potassium hydroxide in methanol
  5. stirringstirred at room temperature for 90 minutes
  6. customThe methanol was removed in vacuo
  7. customthe residue partitioned between ethyl acetate/chloroform (1:1)/water
  8. customthe organic phase dried
  9. customThis material was purified by chromatography on a bond-elut (silica, 2 g)
  10. washeluting with an ethyl acetate/cyclohexane gradient
  11. customto give
  12. customafter evaporation of the solvent N-cyclopropyl-5-fluoro-4′-[5-(hydroxymethyl)-1,3,4-oxadiazol-2-yl]-6-methyl-1,1′-biphenyl-3-carboxamide

출처 및 근거

ORD 기록
ord-08b669cd9c78418e80543fbf2d31ec41
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425555B2

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