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

HRID 1512783Notes

Reaction equation

HRID 1512783 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:8])[C@@H:5]([CH3:7])[NH2:6].[Cl:9][C:10]1[CH:11]=[C:12]([C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:33]=3[NH:32][CH:31]=[C:30]4[CH:34]=O)[N:21]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH:17]([CH3:19])[CH3:18].[OH-].[Na+]>CO>[Cl:9][C:10]1[CH:11]=[C:12]([C:20]2[O:24][N:23]=[C:22]([C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:33]=3[NH:32][CH:31]=[C:30]4[CH2:34][NH:6][C@@H:5]([C:4]([O:3][CH3:2])=[O:8])[CH3:7])[N:21]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH:17]([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 11182647Methyl D-alaninate hydrochlorideHCID 591461517-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde

Product 1

HCID 59146035Methyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-D-alaninateYield 55.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

D-alanine methyl ester hydrochloride (420 mg) and 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde (D71) (382 mg) was added to a solution of NaOH (120 mg) in methanol (20 mL). After stirring for 0.5 hour, methanol was evaporated off. A solution of AcOH (0.5 mL) in dichloromethane (40 mL) was added to the residue. NaBH(OAc)3 (847 mg) was added to the above mixture. The reaction mixture was stirred at room temperature overnight, and quenched by saturated NaHCO3 solution. The organic layer was separated and washed with water and brine. After the solvent was evaporated off the residue was purified by Mass Directed AutoPrep to afford methyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-D-alaninate (D75) (262 mg) as a white solid. MS (ES): C24H25ClN4O4 requires 468; found 491.1 (M+Na+).

Workup

  1. custommethanol was evaporated off
  2. additionA solution of AcOH (0.5 mL) in dichloromethane (40 mL) was added to the residue
  3. additionNaBH(OAc)3 (847 mg) was added to the above mixture
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. customquenched by saturated NaHCO3 solution
  6. customThe organic layer was separated
  7. washwashed with water and brine
  8. customAfter the solvent was evaporated off the residue
  9. customwas purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-5b2221773e5f4f92894237afea9ce9e2
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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