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

Reaktionsgleichung

Reaktionsgleichung von HRID 31478
[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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-dffcb14f41684e11b3c81c2359f9c2d7
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07425555B2

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