1-Hydroxybenzotriazole → N-Cyclopropyl-6-methyl-4'-[5-({[(3-methylisoxazol-5-yl)acetyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1,1'-biphenyl-3-carboxamide

HRID 31478

反応式

HRID 31478 の反応式
[NH2:1][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.C1C=CC2N(O)N=NC=2C=1.[CH3:37][C:38]1[CH:42]=[C:41]([CH2:43][C:44](O)=[O:45])[O:40][N:39]=1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)CCl>[CH:24]1([NH:23][C:21]([C:16]2[CH:15]=[C:14]([C:11]3[CH:10]=[CH:9][C:8]([C:6]4[O:7][C:3]([CH2:2][NH:1][C:44](=[O:45])[CH2:43][C:41]5[O:40][N:39]=[C:38]([CH3:37])[CH:42]=5)=[N:4][N:5]=4)=[CH:13][CH:12]=3)[C:19]([CH3:20])=[CH:18][CH:17]=2)=[O:22])[CH2:26][CH2:25]1

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 41955322-(3-Methyl-1,2-oxazol-5-yl)acetic acidHCID 99978914'-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1'-biphenyl-3-carboxamide

生成物 1

HCID 10479880N-Cyclopropyl-6-methyl-4'-[5-({[(3-methylisoxazol-5-yl)acetyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1,1'-biphenyl-3-carboxamide

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 6228Dimethylformamide溶媒

実験手順

4′-[5-(Aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1′-biphenyl-3-carboxamide (Example 53) (30 mg), EDC (19.8 mg), HOBt (11.7 mg), 3-methyl-5-isoxazoleacetic acid (12.2 mg) and DIPEA (0.02 ml) were mixed in DMF (5 ml). The reaction was stirred at room temperature for 48 hours, the DMF evaporated under vacuum and the residue dissolved in DCM. The solution was washed with water (2×10 ml) and the DCM was evaporated under vacuum. The residue was dissolved in methanol and filtered through a bond-elut (SCX, 2 g). The solvent was evaporated from the filtrate and the residue applied to a bond-elut (silica) and eluted with an ethyl acetate/cyclohexane gradient to give, after evaporation of the solvent, N-cyclopropyl-6-methyl-4′-[5-({[(3-methylisoxazol-5-yl)acetyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1,1′-biphenyl-3-carboxamide.

後処理

  1. customthe DMF evaporated under vacuum
  2. dissolutionthe residue dissolved in DCM
  3. washThe solution was washed with water (2×10 ml)
  4. customthe DCM was evaporated under vacuum
  5. dissolutionThe residue was dissolved in methanol
  6. filtrationfiltered through a bond-elut (SCX, 2 g)
  7. customThe solvent was evaporated from the filtrate
  8. washeluted with an ethyl acetate/cyclohexane gradient
  9. customto give
  10. customafter evaporation of the solvent, N-cyclopropyl-6-methyl-4′-[5-({[(3-methylisoxazol-5-yl)acetyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1,1′-biphenyl-3-carboxamide

出典と根拠

ORDレコード
ord-dffcb14f41684e11b3c81c2359f9c2d7
出典データセット
uspto-grants-2008_09
特許番号
US07425555B2

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