Triethylamine → 6-fluoro-2-(2-methoxyphenyl)-3H-quinazolin-4-one

HRID 1693014Notes

Reaction equation

HRID 1693014 reaction equation
[C:1](Cl)(=O)[C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:14]=1[C:15]([NH2:17])=[O:16].C(N(CC)CC)C>O1CCCC1>[F:22][C:19]1[CH:18]=[C:14]2[C:13](=[CH:21][CH:20]=1)[N:12]=[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH3:9])[NH:17][C:15]2=[O:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 889692-Methoxybenzoyl chlorideHCID 102410032-Amino-5-fluorobenzamide

Product 1

HCID 1361214776-fluoro-2-(2-methoxyphenyl)-3H-quinazolin-4-oneYield 80.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

o-Anisoyl chloride (15.7 g, 92 mmol) was added dropwise to a solution of 2-amino-5-fluorobenzamide (13.0 g, 84 mmol) and triethylamine (16 mL, 110 mmol) in tetrahydrofuran (100 mL) cooled in an ice bath. Immediately a precipitate started forming. Stirring of the solution was continued for 5 hours at room temperature. The formed precipitate was collected by filtration and was washed twice with diethyl ether and dried at 50° C. in vacuo. The dried solid was suspended in 2 N aqueous sodium hydroxide solution (250 mL) and heated at reflux until a clear solution was obtained (3 hours). The reaction mixture was cooled to room temperature and filtered. The filtrate was acidified to pH<1 with concentrated aqueous HCl. The formed precipitate was collected by filtration and washed twice with water, twice with methanol, and twice with diethyl ether. The solid was dried in an oven at 45° C. to yield 6-fluoro-2-(2-methoxyphenyl)-3H-quinazolin-4-one (18.2 g, 80%) as a white solid.

Workup

  1. temperaturecooled in an ice bath
  2. customImmediately a precipitate started forming
  3. filtrationThe formed precipitate was collected by filtration
  4. washwas washed twice with diethyl ether
  5. customdried at 50° C. in vacuo
  6. temperatureheated
  7. temperatureat reflux until a clear solution
  8. customwas obtained (3 hours)
  9. filtrationfiltered
  10. filtrationThe formed precipitate was collected by filtration
  11. washwashed twice with water, twice with methanol
  12. customThe solid was dried in an oven at 45° C.

Sources & evidence

ORD record
ord-538d0eca6ccc4a4d8b1be023477a186c
Source dataset
uspto-grants-2012_04
Patent number
US08158637B2

Reaction notes

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