Phosphorus oxychloride → N-{2-[(4-Chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamide

HRID 1864357Notes

Reaction equation

HRID 1864357 reaction equation
[CH3:1][N:2]([CH2:6][CH2:7][O:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11](=O)[NH:12][CH:13]=[N:14]2)[C:3](=[O:5])[CH3:4].C(N(C(C)C)CC)(C)C.P(Cl)(Cl)([Cl:31])=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[Cl:31][C:11]1[C:10]2[C:15](=[CH:16][CH:17]=[CH:18][C:9]=2[O:8][CH2:7][CH2:6][N:2]([CH3:1])[C:3](=[O:5])[CH3:4])[N:14]=[CH:13][N:12]=1

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 136388298N-methyl-N-{2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]ethyl}acetamide

Product 1

HCID 86615689N-{2-[(4-Chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamideYield 32.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-Methyl-N-{2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]ethyl}acetamide (261 mg, 1.00 mmol) and diiso-propylethylamine (522 μl, 3.00 mmol) were dissolved in DCM (25 ml), and the mixture cooled to 0° C. Phosphorus oxychloride (930 μl, 10 mmol) was added drop wise; the solution was warmed to ambient temperature and stirred for 2 hours. The mixture was cooled to 0° C., and saturated sodium hydrogen carbonate solution (30 ml) was added with vigorous stirring. The stirred mixture was allowed to warm to ambient temperature over 20 minutes. The DCM layer was separated, washed with saturated sodium hydrogen carbonate solution (30 ml), water (30 ml) and brine (30 ml), filtered through a silicone-treated filter paper, and evaporated to give N-{2-[(4-chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamide as an orange solid (90 mg, 32%); NMR Spectrum (DMSO-d6, 400 MHz, CDCl3) 2.05 (s, 3H), 3.17 (s, 3H), 3.85 (t, 2H), 4.28 (t, 2H), 6.99 (d, 1H), 7.58 (d, 1H), 7.76 (dd, 1H), 8.87 (s, 1H); Mass spectrum 276.4 MH+ (4-OMe derivative—product quenched with MeOH in instrument).

Workup

  1. temperaturethe solution was warmed to ambient temperature
  2. temperatureThe mixture was cooled to 0° C.
  3. temperatureto warm to ambient temperature over 20 minutes
  4. customThe DCM layer was separated
  5. washwashed with saturated sodium hydrogen carbonate solution (30 ml), water (30 ml) and brine (30 ml)
  6. filtrationfiltered through a silicone-
  7. additiontreated
  8. filtrationfilter paper
  9. customevaporated

Sources & evidence

ORD record
ord-016017090e7d4367a18f4b5555bd6f8e
Source dataset
uspto-grants-2009_12
Patent number
US07625908B2

Reaction notes

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