Acetic Acid → HCID 69432244, compound

HRID 1269983Notes

Reaction equation

HRID 1269983 reaction equation
[CH2:1]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[C:17]([CH3:25])=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[CH:19]3)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:28](O)(=O)C.C([BH3-])#N.[Na+]>CO.C(Cl)(Cl)Cl>[CH2:1]([N:8]([CH3:28])[C@H:9]1[CH2:14][CH2:13][CH2:12][C@@H:11]([O:15][C:16]2[C:17]([CH3:25])=[C:18]3[C:22](=[CH:23][CH:24]=2)[NH:21][N:20]=[CH:19]3)[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69432503HCID 69432503, compound

Product 1

HCID 69432244HCID 69432244, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Under nitrogen, the N-benzyl-N-[cis-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexyl]amine (150 mg, 0.447 mmol) obtained in Example 716 and 36%-formaldehyde (56 mg, 0.671 mmol) were suspended in methanol (5 ml), followed by adding thereto acetic acid (0.2 ml), and the resulting mixture was stirred at room temperature for 30 minutes. Then, sodium cyanoborohydride (56 mg, 0.894 mmol) was added thereto and the resulting mixture was stirred at room temperature for 17 hours. The reaction mixture was diluted with chloroform and then 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 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, 100/1) to obtain N-benzyl-N-methyl-N-[cis-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexyl]amine (136 mg, yield 87.0%) as a white amorphous substance.

Workup

  1. additionby adding
  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 a saturated aqueous sodium chloride solution
  5. dry with materialdried 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, 100/1)

Sources & evidence

ORD record
ord-b4256a55074e452682dd6397b14b5b0f
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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