Water → HCID 69434092, compound

HRID 1269979Notes

Reaction equation

HRID 1269979 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][N:6]2[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1.Br[CH2:26][CH2:27][CH2:28][CH2:29]Br.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C>[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[CH2:29][CH2:28][CH2:27][CH2:26]3)[CH2:13]2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 69436428HCID 69436428, compound

Product 1

HCID 69434092HCID 69434092, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Under nitrogen, the cis-3-[(4-methyl-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-yl)oxy]cyclohexanamine (100 mg, 0.304 mmol) obtained in Example 724 was dissolved in N,N-dimethylacetamide (3 ml), followed by adding thereto 1,4-dibromobutane (36 μl, 0.304 mmol) and potassium carbonate (105 mg, 0.759 mmol), and the resulting mixture was stirred at 80° C. for 1.5 hours. The reaction solution was cooled to room temperature and water was added thereto, followed by extraction with chloroform (twice). 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, 100/2) to obtain 4-methyl-5-[(cis-3-pyrrolidin-1-ylcyclohexyl)oxy]-1-tetrahydro-2H-pyran-2-yl-1H-indazole (64 mg, yield 55.0%) as light-yellow tar.

Workup

  1. additionby adding
  2. extractionfollowed by extraction with chloroform (twice)
  3. washThe combined chloroform layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried by the addition of anhydrous magnesium sulfate
  5. filtrationfiltered
  6. distillationThe solvent was distilled off under reduced pressure
  7. concentrationthe resulting concentration residue
  8. customwas purified by a silica gel column chromatography (eluent: acetonitrile/aqueous ammonia=100/0, 100/2)

Sources & evidence

ORD record
ord-2d27ea8485a245179324e7d16fee9244
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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