N,N-Diethylaniline → HCID 67282040, compound

HRID 1616117Notes

Reaction equation

HRID 1616117 reaction equation
[CH3:1][N:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:9]=2)[NH:4][C:3]1=O.P(Cl)(Cl)([Cl:20])=O.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:20][C:3]1[N:2]([CH3:1])[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:13]([O:15][CH3:16])=[O:14])[CH:9]=2)[N:4]=1

Participants

5

Reactant 4

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 14116711HCID 14116711, compound

Product 1

HCID 67282040HCID 67282040, compoundYield 26.9%

Conditions

Temperature
120 °C

Procedure

Into a round bottom flask was added methyl 3-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-carboxylate (1.3 g, 5.3 mmol) dissolved in phosphoryl chloride (20.0 mL, 214 mmol). N,N-diethylaniline (2.6 mL, 16.0 mmol) was added followed by phosphorus pentachloride (0.56 g, 2.7 mmol). The reaction mixture was heated to 120° C. and stirred for 1 d. The mixture was then cooled to rt and concentrated. The residue was poured over ice and extracted with DCM (3×). The combined organic phases were then washed with water, and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was purified by flash silica gel chromatography (0% to 50% EtOAc/hexanes) to afford methyl 2-chloro-3-methyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate (0.36 g, 26%). LC-MS: (FA) ES+ 253; 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J=2.0 Hz, 1H), 8.38 (dd, J=8.5, 2.0 Hz, 1H), 7.67 (d, J=8.5 Hz, 1H), 3.97 (s, 3H), 3.78 (s, 3H).

Workup

  1. temperatureThe mixture was then cooled to rt
  2. concentrationconcentrated
  3. additionThe residue was poured over ice
  4. extractionextracted with DCM (3×)
  5. washThe combined organic phases were then washed with water, and brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by flash silica gel chromatography (0% to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8c22002e864f40db9d142c8ba59264aa
Source dataset
uspto-grants-2014_07
Patent number
US08765773B2

Reaction notes

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