Tetrahydrofuran → HCID 9802910, compound

HRID 2303977Notes

Reaction equation

HRID 2303977 reaction equation
O1CCCC1.[NH2:6][C:7]1[C:16]2[CH2:15][N:14]([C:17](=O)[CH2:18][CH:19]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=3)[C:20]([NH:22][CH3:23])=O)[CH2:13][CH2:12][C:11]=2[N:10]=[C:9]2[CH2:33][CH2:34][CH2:35][CH2:36][C:8]=12>CO>[NH2:6][C:7]1[C:16]2[CH2:15][N:14]([CH2:17][CH2:18][CH:19]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=3)[CH2:20][NH:22][CH3:23])[CH2:13][CH2:12][C:11]=2[N:10]=[C:9]2[CH2:33][CH2:34][CH2:35][CH2:36][C:8]=12

Participants

4

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 15524257HCID 15524257, compound

Product 1

HCID 9802910HCID 9802910, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A tetrahydrofuran solution (1 ml) of (±)-10-amino-2-[3-(3,4-dichlorophenyl)-4-methylamino-1,4-dioxobutyl]-1,2,3,4,6,7,8,9-octahydrobenzo[b][1,6]-naphthyridine (55 mg, 0.119 mmol) was added to a tetrahydrofuran solution (0.92N, 2.59 ml, 2.38 mmol) of a borane-tetrahydrofuran complex under cooling with ice water, and the solution was stirred for one hour and then refluxed under heating for 2 hours. The reaction solution was again cooled with ice water, then methanol (2 ml) was added thereto with case, and the solution was stirred for one hour. The reaction solution was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (1 ml), to which 4N hydrogen chloride/dioxane (2 ml) was added under cooling with ice water with care and the mixture was refluxed under heating for one hour. The reaction solution was concentrated and the residue was neutralized with a sodium hydroxide solution and extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (basic silica gel, dichloromethane/methanol=40/1) to obtain the title compound (37.9 mg, 74%) as an colorless oil.

Workup

  1. temperaturerefluxed
  2. temperatureunder heating for 2 hours
  3. stirringwith case, and the solution was stirred for one hour
  4. concentrationThe reaction solution was concentrated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (1 ml), to which 4N hydrogen chloride/dioxane (2 ml)
  6. additionwas added
  7. temperatureunder cooling with ice water with care
  8. temperaturethe mixture was refluxed
  9. temperatureunder heating for one hour
  10. concentrationThe reaction solution was concentrated
  11. extractionextracted with dichloromethane
  12. dry with materialThe obtained organic layer was dried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customthe residue was purified by silica gel column chromatography (basic silica gel, dichloromethane/methanol=40/1)

Sources & evidence

ORD record
ord-66c16f9ca470413b82969d1c41f5939a
Source dataset
uspto-grants-2002_08
Patent number
US06433174B1

Reaction notes

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