Sodium Hydroxide → Ethyl 1-{[6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-4-piperidinecarboxylate

HRID 1512806Notes

Reaction equation

HRID 1512806 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:27]=[C:26]4[C:22]([C:23]([CH:28]=O)=[CH:24][NH:25]4)=[CH:21][CH:20]=3)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12].Cl.[CH2:31]([O:33][C:34]([CH:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)=[O:35])[CH3:32]>CC(O)=O>[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:27]=[C:26]4[C:22]([C:23]([CH2:28][N:39]5[CH2:40][CH2:41][CH:36]([C:34]([O:33][CH2:31][CH3:32])=[O:35])[CH2:37][CH2:38]5)=[CH:24][NH:25]4)=[CH:21][CH:20]=3)[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 18521570Ethyl 4-piperidinecarboxylate hydrochlorideHCID 591461746-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-1H-indole-3-carbaldehyde

Product 1

HCID 58222435Ethyl 1-{[6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-4-piperidinecarboxylateYield 51.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Sodium hydroxide (5.5 mL, 0.5 M in EtOH) was added to a mixture of 6-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-1H-indole-3-carbaldehyde (D102) (200 mg) and piperidine-4-carboxylic acid ethyl ester hydrochloride (507 mg). The reaction mixture was stirred at room temperature for 10 mins, and AcOH (0.5 ml) was added. After the solvent was evaporated, the residue was dissolved in DCM (40 mL). NaBH(OAc)3 (554 mg) was then added in one portion. After stirred overnight, the reaction was quenched with saturated aqueous sodium bicarbonate solution, and extracted with DCM for 3 times. The combined organic solution was washed with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by Mass Directed AutoPrep to afford ethyl 1-{[6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]methyl}-4-piperidinecarboxylate (D103) (140 mg) as a white solid. MS (ES): C27H30ClN5O4 requires 523; found 524.2.

Workup

  1. customAfter the solvent was evaporated
  2. dissolutionthe residue was dissolved in DCM (40 mL)
  3. additionNaBH(OAc)3 (554 mg) was then added in one portion
  4. stirringAfter stirred overnight
  5. customthe reaction was quenched with saturated aqueous sodium bicarbonate solution
  6. extractionextracted with DCM for 3 times
  7. washThe combined organic solution was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationThe dried solution was concentrated
  10. customThe residue was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-4136628895c44b19a3f0e3e2b600419c
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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