Trifluoroacetic acid → 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acid

HRID 923580Notes

Reaction equation

HRID 923580 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[CH:54]=[CH:53][C:16]([C:17]([N:19]([CH2:45][C:46]([O:48]C(C)(C)C)=[O:47])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4[O:31][N:30]=[C:29]([C:32]5[CH:37]=[CH:36][C:35]([C:38]6[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=6)=[CH:34][CH:33]=5)[N:28]=4)=[CH:23][CH:22]=3)=[O:18])=[CH:15][CH:14]=2)=[O:11])=[C:5]([C:55]([F:58])([F:57])[F:56])[CH:4]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([N:19]([CH2:45][C:46]([OH:48])=[O:47])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4[O:31][N:30]=[C:29]([C:32]5[CH:37]=[CH:36][C:35]([C:38]6[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=6)=[CH:34][CH:33]=5)[N:28]=4)=[CH:23][CH:22]=3)=[O:18])=[CH:53][CH:54]=2)=[O:11])=[C:5]([C:55]([F:58])([F:57])[F:56])[CH:4]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71111624tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate

Product 1

HCID 711119502-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acidYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate INT-41 (77.0 mg, 0.097 mmol) in DCM (2 mL) was added TFA (2 mL). The reaction mixture was stirred at room temperature for 1 h. The solvent was concentrated and the residue re-slurried from DCM (4 mL), then washed successively with DCM (2 mL) and isohexanes (2 mL) to afford 56 mg (78%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acid 362. LCMS-ESI (m/z) calculated for C41H33F3N4O6: 734; no ion observed, tR=8.91 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.82 (s, 1H), 10.34 (s, 1H), 8.35-8.04 (m, 4H), 8.04-7.81 (m, 2H), 7.75-7.52 (m, 6H), 7.49-7.30 (m, 5H), 7.26-7.15 (m, 2H), 4.79 (s, 1H), 4.72 (s, 1H), 4.06 (s, 1H), 4.01 (s, 1H), 3.90-3.78 (m, 5H), 2.38 (s, 3H).

Workup

  1. concentrationThe solvent was concentrated
  2. washthe residue re-slurried from DCM (4 mL), then washed successively with DCM (2 mL) and isohexanes (2 mL)

Sources & evidence

ORD record
ord-07450d1419674e988fea794dd870d1fe
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

Loading…