3,4-dihydro-2H-pyran → HCID 69436428, compound

HRID 1269978Notes

Reaction equation

HRID 1269978 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.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>ClCCl.CN1CCCC1=O>[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:20]1[CH2:21][CH2:22][CH2:23][CH2:24][O:19]1

Participants

8

Reactant 5

HCID 80803,4-dihydro-2H-pyranHCID 14798Sodium HydroxideHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 521998p-Toluenesulfonic acid monohydrateHCID 69431191HCID 69431191, compound

Product 1

HCID 69436428HCID 69436428, compoundYield 89.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Under nitrogen, the cis-3-[(4-methyl-1H-indazol-5-yl)oxy]cyclohexanamine (500 mg, 2.04 mmol) obtained in Example 411 was suspended in dichloromethane (10 ml), and 3,4-dihydro-2H-pyran (205 μl, 2.24 mmol) and pyridinium p-toluenesulfonate (51 mg, 0.204 mmol) were added thereto, followed by adding thereto p-toluenesulfonic acid monohydrate (387 mg, 2.04 mmol). N-methyl-2-pyrrolidinone (10 ml) was added thereto to effect dissolution, and the resulting solution was stirred as follows: at room temperature for 17 hours; at 60° C. for 3.5 hours; and then at 80° C. for 10 hours. The reaction solution was cooled to room temperature and a 1N-aqueous sodium hydroxide solution 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 (eluents: chloroform/methanol=20/1 and chloroform/methanol/aqueous ammonia=10/0.8/0.1) to obtain cis-3-[(4-methyl-1-tetrahydro-2H-pyran-2-yl-1H-indazol-5-yl)oxy]cyclohexanamine (602 mg, yield 89.6%) as colorless tar.

Workup

  1. additionby adding
  2. dissolutiondissolution
  3. waitat 60° C. for 3.5 hours
  4. waitand then at 80° C. for 10 hours
  5. extractionfollowed by extraction with chloroform (twice)
  6. washThe combined chloroform layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried by the addition of anhydrous magnesium sulfate
  8. filtrationfiltered
  9. distillationThe solvent was distilled off under reduced pressure
  10. concentrationthe resulting concentration residue
  11. customwas purified by a silica gel column chromatography (eluents: chloroform/methanol=20/1 and chloroform/methanol/aqueous ammonia=10/0.8/0.1)

Sources & evidence

ORD record
ord-7d53349d1cc445298fbf59016a461acb
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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