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

HRID 523272

반응식

HRID 523272 반응식
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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-e2c0956b32fe4fac962701c7e532cfc7
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334290B2

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