Dimethylformamide → 6-bromo-2-(4-hydroxy-3,5-dimethylphenyl)quinazolin-4(3H)-one

HRID 1498760

反応式

HRID 1498760 の反応式
[OH:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]([C:6](O)=O)=[CH:4][C:3]=1[CH3:12].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:24][C:25]1[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][C:26]=1[C:27]([NH2:29])=[O:28]>C(Cl)Cl>[Br:34][C:31]1[CH:30]=[C:26]2[C:25](=[CH:33][CH:32]=1)[N:24]=[C:6]([C:5]1[CH:9]=[C:10]([CH3:11])[C:2]([OH:1])=[C:3]([CH3:12])[CH:4]=1)[NH:29][C:27]2=[O:28]

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 1383874-Hydroxy-3,5-dimethylbenzoic acidHCID 50192712-Amino-5-bromobenzamide

生成物 1

HCID 1360379946-bromo-2-(4-hydroxy-3,5-dimethylphenyl)quinazolin-4(3H)-one収率 94.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 4-hydroxy-3,5-dimethylbenzoic acid (2.00 g, 12.0 mmol) in CH2Cl2 (60.2 mL) cooled to 0-5° C. was added oxalyl chloride (1.47 mL, 16.8 mmol) followed by dropwise addition of DMF (93.3 μL, 1.20 mmol). The mixture was stirred for 1.25 h, the volatiles were removed under vacuum to give crude acid chloride, which was used immediately without further purification. A mixture of 2-amino-5-bromobenzamide (1.99 g, 9.23 mmol) and the acid chloride (crude residue described above) in THE (92.3 mL) was stirred at room temperature for 17 h, then heated at reflux for 4 h. The volatiles were removed under vacuum, the residue was triturated with EtOAc, and filtered to afford the amide (3.02 g, 90%) as a yellow solid. A mixture of the amide (3.01 g, 8.29 mmol), 2 M NaOH (20.0 mL), water (40.0 mL), and MeCN (20.0 mL) was heated at reflux for 15 h, cooled to 5° C., and neutralized with 2 M aqueous HCl. After stirring for 30 min, the white solid was filtered, triturated with acetone, and filtered again to afford 6-bromo-2-(4-hydroxy-3,5-dimethylphenyl)quinazolin-4(3H)-one (2.28 g, 80%). Selected data: 1H NMR (300 MHz, DMSO-d6) δ 8.18 (d, J=2.29 Hz, 1H), 7.93 (dd, J=8.72, 2.42 Hz, 1H), 7.86 (s, 2H), 7.63 (d, J=8.70 Hz, 1H), 5.75 (s, 1H), 2.24 (s, 6H); MS (APCI) m/z 346 [M+H]+.

後処理

  1. customthe volatiles were removed under vacuum
  2. customto give crude acid chloride, which
  3. customwas used immediately without further purification
  4. temperatureheated
  5. temperatureat reflux for 4 h
  6. customThe volatiles were removed under vacuum
  7. customthe residue was triturated with EtOAc
  8. filtrationfiltered

出典と根拠

ORDレコード
ord-98849ff505a84976a73d9c5190e4914c
出典データセット
uspto-grants-2015_12
特許番号
US09199990B2

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