Water → 3-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione

HRID 523272

反応式

HRID 523272 の反応式
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Br:25])[C:20]=1[Cl:26])=[O:17].O>C1COCC1>[Br:25][C:21]1[C:20]([Cl:26])=[C:19]([N:18]2[C:16](=[O:17])[C:15]3[C:14](=[C:30]([F:31])[CH:29]=[CH:28][CH:27]=3)[NH:13][C:2]2=[O:4])[CH:24]=[CH:23][CH:22]=1

参加物

5

反応物 3

HCID 962WaterHCID 94429TriphosgeneHCID 117761114amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide

生成物 1

HCID 1177611123-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione収率 85%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Triphosgene (453 mg, 1.53 mmol) was added in one portion to a solution of amino-N-(3-bromo-2-chlorophenyl)-3-fluorobenzamide (350 mg, 1.019 mmol) in THF (10 mL) at 0° C. The mixture was stirred at room temperature for 1 h, then was cooled to 0° C. and treated with water until no more gas evolution was observed. The mixture was concentrated and the residue was dissolved in EtOAc, washed sequentially with saturated aqueous NaHCO3, water and brine, and dried and concentrated. The residue was purified by column chromatography on silica gel (24 g), eluting with EtOAc-hexanes (gradient from 0-50%), to provide 3-(3-bromo-2-chlorophenyl)-8-fluoroquinazoline-2,4(1H,3H)-dione as a yellow solid (320 mg, 85% yield). Mass spectrum m/z 369, 371 (M+H)+. 1H NMR (400 MHz, chloroform-d) δ 8.54 (br. s., 1H), 7.97 (d, J=8.1 Hz, 1H), 7.77 (dd, J=6.8, 2.6 Hz, 1H), 7.46 (ddd, J=9.8, 8.3, 1.2 Hz, 1H), 7.36-7.29 (m, 2H), 7.24 (td, J=8.0, 4.8 Hz, 1H).

後処理

  1. temperaturewas cooled to 0° C.
  2. concentrationThe mixture was concentrated
  3. dissolutionthe residue was dissolved in EtOAc
  4. washwashed sequentially with saturated aqueous NaHCO3, water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (24 g)
  8. washeluting with EtOAc-hexanes (gradient from 0-50%)

出典と根拠

ORDレコード
ord-e2c0956b32fe4fac962701c7e532cfc7
出典データセット
uspto-grants-2016_05
特許番号
US09334290B2

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