Acetic Acid → HCID 69434568, compound

HRID 1269973Notes

Reaction equation

HRID 1269973 reaction equation
[CH3:1][O:2][C:3]1[C:11]([O:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][C@H:15](N)[CH2:14]2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2.C=O.[C:22]([BH3-])#[N:23].[Na+].[C:26](O)(=O)C.C(Cl)(Cl)[Cl:31]>C(#N)C.CO>[ClH:31].[CH3:1][O:2][C:3]1[C:11]([O:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][C@H:15]([N:23]([CH3:22])[CH3:26])[CH2:14]2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[N:6][NH:7]2

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 6212ChloroformHCID 5003444Sodium cyanoborohydrideHCID 69429700HCID 69429700, compound

Product 1

HCID 69434568HCID 69434568, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

Under nitrogen, the cis-3-[(4-methoxy-1H-indazol-5-yl)oxy]cyclohexanamine (100 mg, 0.383 mmol) obtained in Example 583 and 36%-formaldehyde (160 mg, 1.91 mmol) were suspended in a mixture of acetonitrile (2 ml) and methanol (2 ml), and the resulting suspension was stirred at room temperature for 20 minutes. Then, sodium cyanoborohydride (48 mg, 0.765 mmol) and acetic acid (0.2 ml) were added thereto, and the resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with chloroform, washed successively with a 1N-aqueous sodium hydroxide solution, water and a saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate, and then filtered. The solvent was distilled off under reduced pressure and the resulting concentration residue was purified by a silica gel column chromatography (eluent: chloroform/methanol=20/1, chloroform/methanol/aqueous ammonia=20/1/0.1). The residue purified was dissolved in isopropyl alcohol and a 4N-hydrochloric acid/dioxane solution was added thereto and stirred. Then, the solvent was distilled off under reduced pressure to obtain N-[cis-3-[(4-methoxy-1H-indazol-5-yl)oxy]cyclohexyl]-N,N-dimethylamine monohydrochloride (43 mg, yield 34%).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 5 hours
  2. washwashed successively with a 1N-aqueous sodium hydroxide solution, water
  3. dry with materiala saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate
  4. filtrationfiltered
  5. distillationThe solvent was distilled off under reduced pressure
  6. concentrationthe resulting concentration residue
  7. customwas purified by a silica gel column chromatography (eluent: chloroform/methanol=20/1, chloroform/methanol/aqueous ammonia=20/1/0.1)
  8. customThe residue purified
  9. dissolutionwas dissolved in isopropyl alcohol
  10. additiona 4N-hydrochloric acid/dioxane solution was added
  11. stirringstirred
  12. distillationThen, the solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-99f4ed8bec7e4326a07e39e95b2c9197
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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