Phosphorus oxychloride → 3-Quinolinecarbonitrile, 4-chloro-7-methoxy-5-[(1-methyl-4-piperidinyl)oxy]-

HRID 347440Notes

Reaction equation

HRID 347440 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][N:18]([CH3:21])[CH2:17][CH2:16]1)[CH:9]=[C:8]([O:22][CH3:23])[CH:7]=2)#[N:2].P(Cl)(Cl)([Cl:26])=O>C(#N)C>[Cl:26][C:12]1[C:11]2[C:6](=[CH:7][C:8]([O:22][CH3:23])=[CH:9][C:10]=2[O:14][CH:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[N:5]=[CH:4][C:3]=1[C:1]#[N:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178493321HCID 178493321, compound

Product 1

HCID 210827133-Quinolinecarbonitrile, 4-chloro-7-methoxy-5-[(1-methyl-4-piperidinyl)oxy]-

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-cyano-4-hydroxy-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinoline (313 mg) and phosphoryl chloride (1.8 ml) in acetonitrile (10 ml) was refluxed and stirred for 20 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 dried under high vacuum overnight. The title compound was obtained as a white solid (225 mg, 68%); NMR spectrum: (DMSOd6) 1.80 (m, 2H), 1.98 (m, 2H), 2.18 (s, 3H), 2.27 (m, 2H), 2.58 (m, 2H), 3.94 (s, 3H), 4.72 (m, 1H), 6.92 (d, 1H), 7.09 (d, 1H), 8.93 (s, 1H); Mass spectrum: M+H+ 332.

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. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-db793ead6f5c44418ee91486f7b7883e
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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