Hydrochloric Acid → HCID 68506576, compound

HRID 1714028Notes

Reaction equation

HRID 1714028 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:20][CH:21](OC)OC)[C:8]=2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[CH2:32][NH:33][CH2:34][CH2:35][N:36]([CH3:38])[CH3:37])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[BH4-].[Na+]>C1COCC1>[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[N:9]3[CH2:20][CH2:21][N:33]([CH2:34][CH2:35][N:36]([CH3:37])[CH3:38])[CH2:32][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=4[C:8]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 68510097HCID 68510097, compound

Product 1

HCID 68506576HCID 68506576, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of methyl 3-cyclohexyl-1-(2,2-dimethoxyethyl)-2-[2-({[2-(dimethylamino)ethyl]amino}methyl)phenyl]-1H-indole-6-carboxylate (0.16 M, 1 eq, from Step 3) in THF was added an equal volume of aqueous 1N HCl. The reaction was heated at 60° C. for 2.5 h and after cooling to RT was quenched by addition of NaOH (2N) and extracted into EtOAc (×3). The combined organic extracts were washed with brine before being dried over Na2SO4, filtered and concentrated in vacuo. The residue was re-dissolved in MeOH and acidified to pH 4 with glacial acetic acid. After stirring for 45 min, NaBH4 (8 eq) was added portionwise until cyclisation was complete as evidenced by LC-MS analysis. 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 (Na2SO4), filtered and concentrated in vacuo. The title compound was obtained as a pale yellow oil and taken on without further purification (quant.); MS (ES+) m/z 460 (M+H)+.

Workup

  1. temperatureafter cooling to RT
  2. customwas quenched by addition of NaOH (2N)
  3. extractionextracted into EtOAc (×3)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialbefore being dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was re-dissolved in MeOH
  9. customThe reaction was quenched by addition of sat. aq. NaHCO3
  10. extractionextracted into EtOAc (×3)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialbefore being dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-64678cd7e61e4403a1e26961c6b0a78e
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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