Phosphorus oxychloride → N-(4-chloro-3-cyano-6-methoxy-7-quinolinyl)acetamide

HRID 396186Notes

Reaction equation

HRID 396186 reaction equation
[C:1]([C:3]1[C:12](=O)[C:11]2[C:6](=[CH:7][C:8]([NH:16][C:17](=[O:19])[CH3:18])=[C:9]([O:14][CH3:15])[CH:10]=2)[NH:5][CH:4]=1)#[N:2].P(Cl)(Cl)([Cl:22])=O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[Cl:22][C:12]1[C:11]2[C:6](=[CH:7][C:8]([NH:16][C:17](=[O:19])[CH3:18])=[C:9]([O:14][CH3:15])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:1]#[N:2]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 23438093N-(3-Cyano-6-methoxy-4-oxo-1,4-dihydro-7-quinolinyl)acetamide

Product 1

HCID 23438009N-(4-chloro-3-cyano-6-methoxy-7-quinolinyl)acetamideYield 91.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

An amount of 10 g (0.039 mol) of N-(3-cyano-6-methoxy-4-oxo-1,4-dihydro-7-quinolinyl)acetamide was subsequently stirred in 29 mL (0.31 mol) of phosphorus oxychloride, heated at 100° C. for 0.5 hours, and cooled to 0° C. To this was slowly added a saturated solution of sodium bicarbonate and ethyl acetate. After separation of the layers, the organic layer was washed with saturated brine, dried over sodium sulfate, and evaporated to give a brown solid (9.8 g, 73% yield), mp 230-235° C.; 1H NMR (DMSO-d6) δ 9.77 (s, 11-1), 8.98 (s, 1H), 8.94 (s, 1H), 7.50 (s, 1H), 4.11 (s, 3H), 2.25 (s, 3H); HRMS (EI) m/z 275.0466 (M+1). Analysis for C13H10ClN3O2.0.75H2O: Found: C, 53.99; H, 3.83; N, 14.53. Calcd: C, 53.62; H, 3.68; N, 14.98.

Workup

  1. temperaturecooled to 0° C
  2. customAfter separation of the layers
  3. washthe organic layer was washed with saturated brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated

Sources & evidence

ORD record
ord-82c72e1b20d84263b4c881d50bd37c59
Source dataset
uspto-grants-2003_08
Patent number
US06608048B2

Reaction notes

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