tert-Butylacetic acid → N-Cyclopropyl-4'-(5-{[(3,3-dimethylbutanoyl)amino]methyl}-1,3,4-oxadiazol-2-yl)-6-methyl-1,1'-biphenyl-3-carboxamide

HRID 31483

Reaction equation

HRID 31483 reaction equation
[C:1]([CH2:5][C:6]([OH:8])=O)([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH2:52][CH2:53][C:54]1[O:58][C:57]([C:59]2[CH:64]=[CH:63][C:62]([C:65]3[C:70]([CH3:71])=[CH:69][CH:68]=[C:67]([C:72]([NH:74][CH:75]4[CH2:77][CH2:76]4)=[O:73])[CH:66]=3)=[CH:61][CH:60]=2)=[N:56][N:55]=1>CN(C=O)C>[CH:75]1([NH:74][C:72]([C:67]2[CH:66]=[C:65]([C:62]3[CH:63]=[CH:64][C:59]([C:57]4[O:58][C:54]([CH2:53][NH:52][C:6](=[O:8])[CH2:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[N:55][N:56]=4)=[CH:60][CH:61]=3)[C:70]([CH3:71])=[CH:69][CH:68]=2)=[O:73])[CH2:77][CH2:76]1

Participants

7

Reactant 5

HCID 14057tert-Butylacetic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 99978914'-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1'-biphenyl-3-carboxamide

Product 1

HCID 10003708N-Cyclopropyl-4'-(5-{[(3,3-dimethylbutanoyl)amino]methyl}-1,3,4-oxadiazol-2-yl)-6-methyl-1,1'-biphenyl-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

t-Butylacetic acid (10 mg) and HATU (33 mg) in DMF (1 ml) were stirred for 10 minutes at room temperature. To this solution was added HOBt (11.6 mg), DIPEA (0.45 ml) and 4′-[5-(aminomethyl)-1,3,4-oxadiazol-2-yl]-N-cyclopropyl-6-methyl-1,1′-biphenyl-3-carboxamide (Example 53) (30 mg) in DMF (3 ml) and the reaction stirred at room temperature for 72 hours. The solvent was evaporated under vacuum and the residue dissolved in DCM and washed with water (2×5 ml). The organic phase was reduced to dryness 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-{[(3,3-dimethylbutanoyl)amino]methyl}-1,3,4-oxadiazol-2-yl)-6-methyl-1,1′-biphenyl-3-carboxamide.

Workup

  1. customThe solvent was evaporated under vacuum
  2. dissolutionthe residue dissolved in DCM
  3. washwashed with water (2×5 ml)
  4. customthe residue purified by bond-elut (silica, 5 g)
  5. washeluting with an ethyl acetate/cyclohexane gradient
  6. customby preparative HPLC to give
  7. customafter evaporation of the solvents, N-cyclopropyl-4′-(5-{[(3,3-dimethylbutanoyl)amino]methyl}-1,3,4-oxadiazol-2-yl)-6-methyl-1,1′-biphenyl-3-carboxamide

Sources & evidence

ORD record
ord-ddaaaa38dd20467ba081cbf039f7f27e
Source dataset
uspto-grants-2008_09
Patent number
US07425555B2

Linked notes

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