Potassium Carbonate → HCID 69431031, compound

HRID 1269981Notes

Reaction equation

HRID 1269981 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][O:28][CH2:29][CH2:30]Br.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>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[CH2:30][CH2:29][O: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 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 21521Bis(2-bromoethyl) etherHCID 69436428HCID 69436428, compound

Product 1

HCID 69431031HCID 69431031, compoundYield 76.1%

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 (90 mg, 0.273 mmol) obtained in Example 724 was dissolved in N,N-dimethylacetamide (2 ml), followed by adding thereto bis(2-bromoethyl) ether (34 μl, 0.273 mmol) and potassium carbonate (94 mg, 0.683 mmol), and the resulting mixture was stirred at 80° C. for 6 hours. The reaction solution was cooled to room temperature and a 1N-aqueous sodium hydroxide solution was added thereto, followed by extraction with chloroform (three times). 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 4-methyl-5-[(cis-3-morpholin-4-ylcyclohexyl)oxy]-1-tetrahydro-2H-pyran-2-yl-1H-indazole (83 mg, yield 76.0%) as light-yellow tar.

Workup

  1. additionby adding
  2. extractionfollowed by extraction with chloroform (three times)
  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, 100/1)

Sources & evidence

ORD record
ord-e45071bc3b3d4a18b2545c4662375f04
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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