Phosphorus oxychloride → 4-chloro-3-cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline

HRID 347444Notes

Reaction equation

HRID 347444 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1O)=[C:10]([O:14][CH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)[CH:9]=[C:8]([O:21][CH2:22][CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)[CH:7]=2)#[N:2].P(Cl)(Cl)([Cl:33])=O>C(#N)C>[Cl:33][C:12]1[C:11]2[C:6](=[CH:7][C:8]([O:21][CH2:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:9][C:10]=2[O:14][CH:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:5]=[CH:4][C:3]=1[C:1]#[N:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1785103203-cyano-4-hydroxy-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline

Product 1

HCID 210827124-chloro-3-cyano-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-cyano-4-hydroxy-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinoline (500 mg) and phosphoryl chloride (2.5 ml) in acetonitrile (1.5 ml) was refluxed and stirred for 4 hours. After cooling, the solution was evaporated to dryness. The flask containing the residue was filled with ice chips and excess concentrated aqueous ammonia (25 ml) was added. This mixture was allowed to warm up while stirring overnight. The product was filtered off and air-dried. The title compound was obtained as a white solid (480 mg, 92%); Mass spectrum: M+H+ 432.

Workup

  1. temperaturewas refluxed
  2. temperatureAfter cooling
  3. customthe solution was evaporated to dryness
  4. additionThe flask containing the residue
  5. additionwas filled with ice chips and excess concentrated aqueous ammonia (25 ml)
  6. additionwas added
  7. temperatureto warm up
  8. stirringwhile stirring overnight
  9. filtrationThe product was filtered off
  10. customair-dried

Sources & evidence

ORD record
ord-a0c8990384e444f2896d5979db1e0721
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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