Hydrochloric Acid → 1-(Cyclohexyl)methyl-3-{5-[(dimethylamino)methyl]-[1,2,4]oxadiazol-3-yl}-7-methoxy-1H-indole, hydrochloride salt

HRID 644019Notes

Reaction equation

HRID 644019 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]([NH:21][OH:22])=[NH:20])=[CH:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].CO[C:27](=O)[CH2:28][N:29]([CH3:31])[CH3:30].[ClH:33]>O1CCCC1.C(O)(C)C>[ClH:33].[CH:1]1([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[O:17][CH3:18])[C:10]([C:19]3[N:20]=[C:27]([CH2:28][N:29]([CH3:31])[CH3:30])[O:22][N:21]=3)=[CH:9]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 81569Glycine, N,N-dimethyl-, methyl esterHCID 178488697HCID 178488697, compound

Product 1

HCID 1317280661-(Cyclohexyl)methyl-3-{5-[(dimethylamino)methyl]-[1,2,4]oxadiazol-3-yl}-7-methoxy-1H-indole, hydrochloride salt

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Molecular sieves (4 Å, powdered, 200 mg) were added to a suspension of 1-(cyclohexyl)methyl-N-hydroxy-7-methoxy-1H-indole-3-carboxamidine (250 mg, 0.829 mmol) in tetrahydrofuran (6 ml) under nitrogen, and the mixture was stirred at room temperature for 30 min. Sodium hydride (60% suspension in oil, 36 mg, 0.900 mmol) was added, then the resulting mixture was stirred at 60° C. for 20 min. The reaction mixture was cooled to room temperature and N,N-dimethylglycine methyl ester (194 mg, 1.66 mmol) was added to the mixture. The resulting mixture was stirred at reflux temperature for 2 h and then concentrated in vacuo. The obtained residue was mixed with dichloromethane (200 ml), washed with 5% aqueous sodium carbonate, dried over magnesium sulfate and concentrated in vacuo. The obtained oil was purified by flash column chromatography eluting with 0.6% (v/v) methanol in dichloromethane to afford an oil. This oil was dissolved in isopropanol (3 ml), then hydrogen chloride (1M solution in diethyl ether; 3 ml) was added to the solution. The resulting mixture was concentrated in vacuo to afford the title compound (1:1 hydrochloride salt) (66 mg).

Workup

  1. stirringthe resulting mixture was stirred at 60° C. for 20 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringThe resulting mixture was stirred
  4. temperatureat reflux temperature for 2 h
  5. concentrationconcentrated in vacuo
  6. additionThe obtained residue was mixed with dichloromethane (200 ml)
  7. washwashed with 5% aqueous sodium carbonate
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe obtained oil was purified by flash column chromatography
  11. washeluting with 0.6% (v/v) methanol in dichloromethane
  12. customto afford an oil
  13. concentrationThe resulting mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-0a389457b76a4387b11720557bf39873
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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