Glycolic Acid → N-Cyclopropyl-4'-{5-[(glycoloylamino)methyl]-1,3,4-oxadiazol-2-yl}-6-methyl-1,1'-biphenyl-3-carboxamide

HRID 31484

Reaction equation

HRID 31484 reaction equation
[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.CCN(C(C)C)C(C)C.[C:46](O)(=[O:49])[CH2:47][OH:48]>C(Cl)Cl.CO.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:47](=[O:48])[CH2:46][OH:49])=[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

Participants

8

Reactant 4

HCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 99978914'-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1'-biphenyl-3-carboxamide

Product 1

HCID 11742059N-Cyclopropyl-4'-{5-[(glycoloylamino)methyl]-1,3,4-oxadiazol-2-yl}-6-methyl-1,1'-biphenyl-3-carboxamide

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

4′-[5-(Aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1′-biphenyl-3-carboxamide (Example 53) (30 mg), HOBt (11.7 mg), EDC (19.8 mg), DIPEA (0.018 ml) and glycolic acid (6.6 mg) were mixed in DCM (6 ml) and methanol (1 ml) and the reactions stirred at room temperature for 96 hours. The reaction was reduced to dryness under vacuum and the residue partitioned between DCM and water. The organic phase was evaporated and the residue purified by bond-elut (silica, 5 g) eluting with an ethyl acetate/cyclohexane gradient and then by preparative HPLC to give, after evaporation of the solvents, N-cyclopropyl-4′-{5-[(glycoloylamino)methyl]-1,3,4-oxadiazol-2-yl}-6-methyl-1,1′-biphenyl-3-carboxamide.

Workup

  1. customthe residue partitioned between DCM and water
  2. customThe organic phase was evaporated
  3. customthe residue purified by bond-elut (silica, 5 g)
  4. washeluting with an ethyl acetate/cyclohexane gradient
  5. customby preparative HPLC to give
  6. customafter evaporation of the solvents, N-cyclopropyl-4′-{5-[(glycoloylamino)methyl]-1,3,4-oxadiazol-2-yl}-6-methyl-1,1′-biphenyl-3-carboxamide

Sources & evidence

ORD record
ord-185c1fae696745f7b51017f6b1de24bf
Source dataset
uspto-grants-2008_09
Patent number
US07425555B2

Linked notes

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