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

HRID 923570Notes

Reaction equation

HRID 923570 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[N:31]=[C:30]([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)[O:29][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[N:31]=[C:30]([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)[O:29][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 71112076tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate

Product 1

HCID 711116302-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acidYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 8: To a stirring solution of tert-butyl 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetate INT-34 (54.0 mg, 0.068 mmol) in DCM (2 mL) was added TFA (2 mL). After stirring at room temperature for 2 h, the solvent was concentrated and the reaction mixture was further concentrated from acetonitrile (2×3 mL). The solid was re-slurried from DCM (4 mL), washed with DCM (2 mL) and acetonitrile (2 mL) to afford 44 mg (87%) of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 354. LCMS-ESI (m/z) calculated for C41H33F3N4O6: 734; found 735 [M+H]+, tR=9.40 min (Method 9). 1H NMR (400 MHz, DMSO) δ 12.80 (s, 1H), 10.34 (s, 1H), 8.33-8.22 (m, 2H), 8.15-8.06 (m, 2H), 8.02-7.91 (m, 2H), 7.76-7.69 (m, 2H), 7.69-7.56 (m, 3H), 7.53-7.33 (m, 6H), 7.26-7.14 (m, 2H), 4.77 (s, 1H), 4.69 (s, 1H), 4.04 (s, 1H), 3.98 (s, 1H), 3.90-3.77 (m, 5H), 2.39 (s, 3H).

Workup

  1. customPrepared
  2. concentrationthe solvent was concentrated
  3. concentrationthe reaction mixture was further concentrated from acetonitrile (2×3 mL)
  4. washwashed with DCM (2 mL) and acetonitrile (2 mL)

Sources & evidence

ORD record
ord-636c0be6f6944cb6b0f90cbd11c20b23
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

Loading…