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

HRID 336776

반응식

HRID 336776 반응식
[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.C1COCC1>[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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 THF (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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-dacba69a102b454394a8560314b2b376
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889698B2

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