Phosphorus oxychloride → HCID 89782281, compound

HRID 1056121Notes

Reaction equation

HRID 1056121 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[N:8]([CH3:13])[C:7]2=[O:14].P(Cl)(Cl)([Cl:17])=O.C(N(C(C)C)C(C)C)C>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([Cl:17])[N:8]([CH3:13])[C:7]2=[O:14]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 84804835HCID 84804835, compound

Product 1

HCID 89782281HCID 89782281, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A slurry of 8-bromo-3-methylquinazoline-2,4(1H,3H)-dione (722b, 1.14 g, 4.47 mmol), phosphoryl trichloride (4.09 mL, 44.7 mmol), and N-ethyl-N-isopropylpropan-2-amine (3.11 mL, 17.88 mmol) was stirred at reflux for 19 h. The reaction mixture was concentrated, diluted with ice, basicified with 10 N NaOH to ˜pH 10, filtered, and washed with water to give brown solid. The solid was transferred to an Erlenmeyer flask and dissolved in DCM when a small aqueous layer formed; this was partitioned in a separatory funnel. The organic layer was partially concentrated, loaded onto the column and was purified via automated flash chromatography (silica gel) with 0-40% EtOAc in hexanes to give 8-bromo-2-chloro-3-methylquinazolin-4(3H)-one (722) (1.03 g, 3.77 mmol, 84% yield) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.77 (s, 3H) 7.35 (t, J=7.92 Hz, 1H) 8.02 (dd, J=7.82, 1.37 Hz, 1H) 8.21 (dd, J=8.02, 1.37 Hz, 1H). MS (ESI, pos. ion) m/z: 273.9/275.9 (M+1).

Workup

  1. temperatureat reflux for 19 h
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with ice
  4. filtrationfiltered
  5. washwashed with water
  6. customto give brown solid
  7. customformed
  8. customthis was partitioned in a separatory funnel
  9. concentrationThe organic layer was partially concentrated
  10. customwas purified

Sources & evidence

ORD record
ord-ca9411e3d3c742d9b724f586ad9b4601
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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