Sodium Hydroxide → N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}glycine

HRID 1512915Notes

Reaction equation

HRID 1512915 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][NH:28][CH2:29][C:30]([O:32]CC)=[O:31])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>O1CCCC1.C(O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4[CH2:27][NH:28][CH2:29][C:30]([OH:32])=[O:31])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 59146143HCID 59146143, compound

Product 1

HCID 44548733N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}glycineYield 56.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of ethyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}glycinate (D77) (283 mg) in tetrahydrofuran (5 mL) and ethanol (5 mL) stirred at 20° C. was added a solution of sodium hydroxide (40 mg) in water (5 mL) in one charge. The reaction mixture was stirred at 20° C. overnight. The reaction mixture was concentrated to about 5 mL and then H2SO4 (0.1 M) solution was added dropwise until no further white precipitate was formed. The solid was filtered and washed with EtOAc. The solid was collected and then was suspended in methanol (5 mL). The mixture was acidified with HCl (1 M) solution to pH around 1 to form a clear solution. After most of the solvent was evaporated off, the residue was freeze-dried to afford N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}glycine (E56) (150 mg) as a hydrochloride salt. δH (DMSO-d6, 400 MHz): 1.37 (6H, d), 3.72 (3H, s), 3.85 (2H, s), 4.39 (2H, s), 4.87-4.93 (1H, m), 7.30 (1H, t), 7.47 (1H, d), 7.52 (1H, d), 7.62 (1H, s), 8.05 (1H, s), 8.14 (1H, dd), 8.21 (1H, d), 9.23 (1H, br s). MS (ES): C23H23ClN4O4 requires 454; found 380.1 (M—NHCH2COOH+).

Workup

  1. additioncharge
  2. concentrationThe reaction mixture was concentrated to about 5 mL
  3. additionH2SO4 (0.1 M) solution was added dropwise until no further white precipitate
  4. customwas formed
  5. filtrationThe solid was filtered
  6. washwashed with EtOAc
  7. customThe solid was collected
  8. customto form a clear solution
  9. customAfter most of the solvent was evaporated off
  10. customthe residue was freeze-dried

Sources & evidence

ORD record
ord-9d02ff80236940eba471806397d11e41
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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