Methanol → 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acid

HRID 923608Notes

Reaction equation

HRID 923608 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][C:12]([NH:14][C:15]1[CH:56]=[CH:55][C:18]([C:19]([N:21]([CH2:47][C:48]([O:50]C(C)(C)C)=[O:49])[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[O:33][N:32]=[C:31]([C:34]4[CH:39]=[CH:38][C:37]([C:40]5[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=5)=[CH:36][CH:35]=4)[N:30]=3)=[CH:25][CH:24]=2)=[O:20])=[CH:17][CH:16]=1)=[O:13].CO.[Li+].[OH-]>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11][C:12]([NH:14][C:15]1[CH:56]=[CH:55][C:18]([C:19]([N:21]([CH2:47][C:48]([OH:50])=[O:49])[CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[O:33][N:32]=[C:31]([C:34]4[CH:39]=[CH:38][C:37]([C:40]5[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=5)=[CH:36][CH:35]=4)[N:30]=3)=[CH:25][CH:24]=2)=[O:20])=[CH:17][CH:16]=1)=[O:13]

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 71111955tert-butyl 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate

Product 1

HCID 711116462-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acidYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared using General Procedure 9. To a stirring solution of tert-butyl 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate INT-65 (55 mg, 0.073 mmol) in THF (2 mL) and MeOH (0.25 mL) was added 1 M LiOH (146 μL, 0.146 mmol). The reaction mixture was stirred at room temperature for 20 h and a precipitate was formed. The mixture was filtered under vacuum and the captured solid washed with diethyl ether (5 mL). The captured solid was under vacuum to provide 36 mg (71%) of 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetic acid 457 as a white solid. LCMS-ESI (m/z) calculated for C41H36N4O7: 696; found 697 [M+H]+, tR=9.84 min (Method 9). 1H NMR (400 MHz, DMSO) δ 9.89 (s, 1H), 8.22-8.11 (m, 4H), 7.87 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.1 Hz, 2H), 7.60 (d, J=8.6 Hz, 4H), 7.51 (d, J=8.0 Hz, 2H), 7.33 (d, J=7.9 Hz, 2H), 6.94-6.90 (m, 1H), 6.88 (d, J=3.1 Hz, 1H), 6.83-6.78 (m, 1H), 4.81 (s, 2H), 3.75 (s, 3H), 3.72 (s, 3H), 3.64 (s, 2H), 3.48 (s, 2H), 2.39 (s, 3H).

Workup

  1. customPrepared
  2. customa precipitate was formed
  3. filtrationThe mixture was filtered under vacuum
  4. washthe captured solid washed with diethyl ether (5 mL)

Sources & evidence

ORD record
ord-43bdd877b6b34b59938f2bbf57309fab
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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