Acetic Acid → HCID 69431488, compound

HRID 1269977Notes

Reaction equation

HRID 1269977 reaction equation
[CH3:1][C:2]1[C:10]([O:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([NH2:18])[CH2:13]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH:19](=O)[CH2:20][CH2:21][CH2:22][CH:23]=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO.C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:10]([O:11][C@H:12]2[CH2:17][CH2:16][CH2:15][C@@H:14]([N:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH2:13]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 3485GlutaraldehydeHCID 5003444Sodium cyanoborohydrideHCID 69431191HCID 69431191, compound

Product 1

HCID 69431488HCID 69431488, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Under nitrogen, the cis-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanamine (100 mg, 0.403 mmol) obtained in Example 411 and 25%-glutaraldehyde (187 mg, 0.448 mmol) were dissolved in methanol (10 ml), and the resulting solution was stirred at room temperature for 40 minutes. Then, sodium cyanoborohydride (51 mg, 0.815 mmol) and acetic acid (0.2 ml) were added thereto, and the resulting mixture was stirred at room temperature for 16 hours. The reaction solution was diluted with chloroform and separated by the addition of a 1N-aqueous sodium hydroxide solution, and the desired compound was further extracted from the aqueous layer with chloroform. The combined chloroform layer was washed with water and then 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: acetonitrile/aqueous ammonia=100/0, 100/2, 100/4) to obtain 4-methyl-5-[(cis-3-piperidin-1-ylcyclohexyl)oxy]-1H-indazole (91 mg, yield 71.2%) as a white amorphous substance.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 16 hours
  2. customseparated by the addition of a 1N-aqueous sodium hydroxide solution
  3. extractionthe desired compound was further extracted from the aqueous layer with chloroform
  4. washThe combined chloroform layer was washed with water
  5. dry with materiala saturated aqueous sodium chloride solution, dried by the addition of anhydrous magnesium sulfate
  6. filtrationfiltered
  7. distillationThe solvent was distilled off under reduced pressure
  8. concentrationthe resulting concentration residue
  9. customwas purified by a silica gel column chromatography (eluent: acetonitrile/aqueous ammonia=100/0, 100/2, 100/4)

Sources & evidence

ORD record
ord-9ad2d8284fe6484a80298b63dea1512c
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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