Toluene → 4,6-Dichloroquinazoline

HRID 2225167Notes

Reaction equation

HRID 2225167 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2O.P(Cl)(Cl)([Cl:15])=O.C(N(CC)CC)C.C1(C)C=CC=CC=1>C(Cl)Cl>[Cl:15][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=2)[N:8]=[CH:7][N:6]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178518001HCID 178518001, compound

Product 1

HCID 2460244,6-Dichloroquinazoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Preparation D1, Step 2: 6-Chloroquinazolin-4-ol (400 mg, 2.21 mmol, 1 eq.), phosphorus oxychloride (1.99 mL, 21.4 mmol, 9.64 eq.) and triethylamine (0.99 mL, 7.11 mmol, 3.21 eq.) were mixed at room temperature under nitrogen and then refluxed for 2.5 hours. Worked up by stripping the reaction, then re-rotovapping the residue 2 times from toluene to obtain brown solids. Methylene chloride (25 mL) was added to dissolve the solids. The organic mixture was then rinsed 2 times with saturated ammonium chloride (25 mL). The organic layer was dried (sodium sulfate) and stripped to give brown solids. The solids were purified over silica gel in 9:1 to 3:1 hexanes/ethyl acetate. Obtained 4,6-dichloroquinazoline (300 mg) as an off-white solid. Yield=68%. 1H NMR (400 MHz) (DMSO-D6) δ 9.16 (s, 1H): 8.33 (s, 1H), 8.17 (apparent t, 2H, J=7 Hz).

Workup

  1. temperaturerefluxed for 2.5 hours
  2. customthe reaction
  3. customto obtain brown solids
  4. dissolutionto dissolve the solids
  5. washThe organic mixture was then rinsed 2 times with saturated ammonium chloride (25 mL)
  6. dry with materialThe organic layer was dried (sodium sulfate)
  7. customto give brown solids
  8. customThe solids were purified over silica gel in 9:1 to 3:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-04e8658a3cf9406a8b55ad75e1b97a98
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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