Hydrochloric Acid → 5-(3-Benzyl-pyrrolidine-3-carbonyl)-1H-indole-3-carbonitrile

HRID 1895001Notes

Reaction equation

HRID 1895001 reaction equation
Cl.C(OC([N:9]1[CH2:13][CH2:12][C:11]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][CH:20]=[C:19]3[C:25]#[N:26])=[O:15])[CH2:10]1)=O)(C)(C)C>CO>[CH2:27]([C:11]1([C:14]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][CH:20]=[C:19]3[C:25]#[N:26])=[O:15])[CH2:12][CH2:13][NH:9][CH2:10]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 666876893-benzyl-3-(3-cyano-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 597447375-(3-Benzyl-pyrrolidine-3-carbonyl)-1H-indole-3-carbonitrileYield 32.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of HCl (1.0 M in MeOH, 8 mL) was slowly added at 0° C. to a solution of 3-benzyl-3-(3-cyano-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (169 mg, 0.393 mmol) in MeOH (2 mL). The resulting pale yellow mixture was stirred at room temperature for 4 hours, then was quenched by addition of 0° C. aqueous NaOH (1.0 M). The resulting mixture was diluted with water and extracted with DCM. The combined organic extracts were dried over MgSO4, filtered and evaporated under reduced pressure. The crude was purified by flash chromatography (MeOH in DCM with 0.5% of NH4OH) to give 42 mg of 5-(3-Benzyl-pyrrolidine-3-carbonyl)-1H-indole-3-carbonitrile as a white foamy solid. This product was dissolved in DCM and a solution of HCl (1.0 M in Et20, 1 equivalent) was added. MeOH was added and the resulting mixture was evaporated under reduced pressure. The residue was triturated with Et2O and 32 mg of 5-(3-benzyl-pyrrolidine-3-carbonyl)-1H-indole-3-carbonitrile hydrochloride was collected as a white solid; MS=330 [M+H]+.

Workup

  1. customwas quenched by addition of 0° C. aqueous NaOH (1.0 M)
  2. additionThe resulting mixture was diluted with water
  3. extractionextracted with DCM
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude was purified by flash chromatography (MeOH in DCM with 0.5% of NH4OH)

Sources & evidence

ORD record
ord-91d678f3f5394e65b5131ad005a4fe22
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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