Triethylamine → 4-Quinazolinamine, N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-

HRID 1881671Notes

Reaction equation

HRID 1881671 reaction equation
[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][NH:6][C:5]2=O.P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[Cl:25][C:26]1[CH:27]=[C:28]([CH:30]=[CH:31][C:32]=1[O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1)[NH2:29]>C(#N)C.C1(C)C=CC=CC=1>[I:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:29][C:28]1[CH:30]=[CH:31][C:32]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)=[C:26]([Cl:25])[CH:27]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 1354016666-Iodoquinazolin-4-one

Product 1

HCID 101745194-Quinazolinamine, N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-Yield 98.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

In a 200 mL-volume glass vessel equipped with a stirrer, a thermometer and a reflux condenser were placed 9.80 g (36 mmol) of 6-iodoquinazolin-4-one, 6.63 g (43 mmol) of phosphorus oxychloride, and 30 mL of toluene in a nitrogen atmosphere. While the mixture was stirred at room temperature, 4.41 g (8.8 mmol) of triethylamine was slowly added. The resulting mixture was heated to 75° C., and then reaction was carried out at 70-80° C. for 3 hours. Subsequently, the mixture was cooled to room temperature, and 40 mL of acetonitrile and 11.8 mg (43 mmol) of 3-chloro-4-(3-fluorobenzyloxy)aniline were added. The resulting mixture was stirred at 70-80° C. for 2 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, and thus precipitated crystalline product was collected by filtration and washed with 20 mL of acetonitrile. Subsequently, the crystalline product was placed in 80 mL of aqueous sodium hydroxide (1 mol/L), and the aqueous mixture was stirred for 2 hours at room temperature. The crystalline product was collected by filtration, washed with 500 mL of water and 20 mL of acetonitrile, and dried under reduced pressure, to give 18.0 g (isolated yield: 98%, purity 100% in terms of area percentage determined by high performance liquid chromatography) of 6-iodo-4-[3-chloro-4-(3-fluorobenzyloxy)anilino]quinazoline as a yellowish crystalline product.

Workup

  1. customIn a 200 mL-volume glass vessel equipped with a stirrer
  2. temperatureThe resulting mixture was heated to 75° C.
  3. customreaction
  4. temperatureSubsequently, the mixture was cooled to room temperature
  5. stirringThe resulting mixture was stirred at 70-80° C. for 2 hours
  6. temperaturethe reaction mixture was cooled to room temperature
  7. filtrationthus precipitated crystalline product was collected by filtration
  8. washwashed with 20 mL of acetonitrile
  9. stirringthe aqueous mixture was stirred for 2 hours at room temperature
  10. filtrationThe crystalline product was collected by filtration
  11. washwashed with 500 mL of water and 20 mL of acetonitrile
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-c01d80a93f424ba7874bbe13764badcb
Source dataset
uspto-grants-2012_11
Patent number
US08318932B2

Reaction notes

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