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

HRID 1512923Notes

Reaction equation

HRID 1512923 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][CH2:28][NH:29][CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C1COCC1>[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][CH2:28][NH:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146046ethyl N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-beta-alaninate

Product 1

HCID 44548892N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-beta-alanineYield 79.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-β-alaninate (D90) (20 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 50° C. for 3 h. The mixture was cooled to room temperature and acidified with aqueous HCl (2 M) to pH 4-5, and then partitioned between ethyl acetate (25 mL) and water (20 mL). The organic phase was evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford N-{2-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]ethyl}-β-alanine (E65) (15 mg, TFA salt). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 2.61 (2H, t), 3.06 (2H, t), 3.20 (4H, m), 3.65 (3H, s), 4.88 (1H, m), 7.22 (1H, t), 7.31 (1H, s), 7.45 (2H, m), 7.83 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d). MS (ES): C25H27ClN4O4 requires 482; found 483.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (25 mL) and water (20 mL)
  3. customThe organic phase was evaporated
  4. customto give the crude product, which
  5. customwas purified by Mass Directed Auto Prep

Sources & evidence

ORD record
ord-9203f7d681d649a3b90aae686e7f91ab
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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