Hydrochloric Acid → Methyl 14-cyclohexyl-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxylate

HRID 1714058Notes

Reaction equation

HRID 1714058 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[N:11]([CH2:29][CH:30]2OCCO2)[C:12]2[C:17]([C:18]=1[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[CH:16][CH:15]=[C:14]([C:25]([O:27][CH3:28])=[O:26])[CH:13]=2.[OH-].[Na+].CO.[BH3-]C#N.[Na+]>C1COCC1.C(O)(=O)C>[CH:19]1([C:18]2[C:17]3[CH:16]=[CH:15][C:14]([C:25]([O:27][CH3:28])=[O:26])=[CH:13][C:12]=3[N:11]3[CH2:29][CH2:30][NH:2][CH2:3][C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=4[C:10]=23)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 68508525methyl 2-[2-(aminomethyl)phenyl]-3-cyclohexyl-1-(1,3-dioxolan-2-ylmethyl)-1H-indole-6-carboxylate

Product 1

HCID 68505807Methyl 14-cyclohexyl-5,6,7,8-tetrahydroindolo[2,1-a][2,5]benzodiazocine-11-carboxylateYield 46%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

3M aqueous HCl (16 eq) was added to a solution of methyl 2-[2-(aminomethyl)phenyl]-3-cyclohexyl-1-(1,3-dioxolan-2-ylmethyl)-1H-indole-6-carboxylate in THF (0.03 M). The reaction was heated with stirring at reflux for 24 h, before being allowed to cool to RT, basified with aqueous NaOH (2N) and extracted into EtOAc (3 times). The combined organics were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo to afford the crude intermediate as a yellow oil. This oil was taken up immediately in MeOH (0.1 M, 1 eq) and the solution acidified to pH 4 with glacial acetic acid. After stirring for 20 min, NaCNBH3 (1.3 eq) was added and the reaction stirred for a further 1 h. The reaction was quenched by addition of sat. aq. NaHCO3 and extracted into EtOAc (×3). The combined organic extracts were washed with brine before being dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (2.5% MeOH/0.5% Et3N/CH2Cl2) gave the title compound as a pale yellow solid (46%); MS (ES+) m/z 389 (M+H)+

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 24 h
  3. extractionextracted into EtOAc (3 times)
  4. washThe combined organics were washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford the crude intermediate as a yellow oil
  9. stirringAfter stirring for 20 min
  10. stirringthe reaction stirred for a further 1 h
  11. customThe reaction was quenched by addition of sat. aq. NaHCO3
  12. extractionextracted into EtOAc (×3)
  13. washThe combined organic extracts were washed with brine
  14. dry with materialbefore being dried over Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. customPurification by flash column chromatography (2.5% MeOH/0.5% Et3N/CH2Cl2)

Sources & evidence

ORD record
ord-159b5829ecdb4e87a2183f788567a2c8
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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