Triethylamine → 4,6-Dichloro-2-propylquinazoline

HRID 2225178Notes

Reaction equation

HRID 2225178 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH2:13][CH3:14])[N:6]=[C:5]2O.P(Cl)(Cl)([Cl:18])=O.C(N(CC)CC)C>C(Cl)Cl>[Cl:18][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=2)[N:8]=[C:7]([CH2:12][CH2:13][CH3:14])[N:6]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178440201HCID 178440201, compound

Product 1

HCID 210882734,6-Dichloro-2-propylquinazolineYield 58.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Preparation D10, Step 3: 6-Chloro-2-propylquinazolin-4-ol (810 mg, 3.64 mmol, 1 eq), phosphorus oxychloride (3.30 mL, 35.1 mmol, 9.64 eq) and triethylamine (1.63 mL, 11.7 mmol, 3.21 eq) were mixed at room temperature then refluxed for 2.5 hours. The reaction was stripped 3 times from methylene chloride. The residue was dissolved in methylene chloride (25 mL) and rinsed 3 times with saturated sodium bicarbonate (25 mL), 1× with water (25 mL). The organic layer was dried (sodium sulfate) and stripped to an amber oil. Purified over silica gel in 9:1 hexanes/ethyl acetate to give 4,6-dichloro-2-propylquinazoline (510 mg) as a light-amber solid. Yield=58%. 1H NMR (400 MHz) (CD3OD) □ 7.98 (s, 1H); 7.98 (d, 1H, J=7 Hz); 7.93 (d, 1H, J=7 Hz); 3.00 (t, 2H, J=7 Hz); 1.90 (t of q, 2 H, J=7 Hz); 1.00 (t, 3H, J=7 Hz).

Workup

  1. customPreparation D10, Step 3
  2. temperaturethen refluxed for 2.5 hours
  3. washrinsed 3 times with saturated sodium bicarbonate (25 mL), 1× with water (25 mL)
  4. dry with materialThe organic layer was dried (sodium sulfate)
  5. customPurified over silica gel in 9:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-8af82a4e83cd4680b9dbbf41ded0a560
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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