Potassium Carbonate → ethyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-beta-alaninate

HRID 1512781Notes

Reaction equation

HRID 1512781 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[NH:24][CH:23]=[C:22]4[CH:26]=O)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].Cl.[NH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].[OH-].[Na+].C([O-])([O-])=O.[K+].[K+]>C(O)C.CC(O)=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[NH:24][CH:23]=[C:22]4[CH2:26][NH:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 591461517-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde

Product 1

HCID 59146098ethyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-beta-alaninateYield 36.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 702EthanolSolvent2×

Procedure

7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde (D71) (381 mg) and ethyl β-alaninate hydrochloride (246 mg) were added to a solution of NaOH (27 mg) in ethanol (20 mL), followed by addition of AcOH (3 mL). Under stirring NaBH3CN (50 mg) in ethanol (2 mL) was added dropwise. The reaction mixture was stirred at room temperature overnight and then basified to pH ˜9 by K2CO3 solution. The mixture was concentrated and EtOAc (50 mL) was added. 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 ethyl N-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-β-alaninate (D72) (176 mg) as a yellow solid. δH (DMSO-d6, 400 MHz): 1.16 (3H, t), 1.38 (6H, d), 2.47 (2H, t), 2.80 (2H, t), 3.90 (2H, s), 4.04 (2H, q), 4.88-4.94 (1H, m), 7.21 (1H, t), 7.37 (1H, t), 7.46 (1H, d), 7.89 (1H, d), 7.94 (1H, dd), 8.22 (1H, dd), 8.39 (1H, d), 10.89 (1H, s).

Workup

  1. concentrationThe mixture was concentrated
  2. additionEtOAc (50 mL) was added
  3. customThe organic layer was separated
  4. washwashed with water and brine
  5. customAfter the solvent was evaporated off the residue
  6. customwas purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-baf53bbb48624630944bc4aa2315bf6a
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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