Chlorosulfanyl isocyanate → 1-Cyclopropyl-6,7-difluoroquinazoline-2,4(1H,3H)-dione

HRID 10320노트

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HRID 10320 반응식
C(O[C:4](=[O:17])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=1[NH:13][CH:14]1[CH2:16][CH2:15]1)C.ClS[N:20]=[C:21]=[O:22]>ClCCl>[CH:14]1([N:13]2[C:6]3[C:5](=[CH:10][C:9]([F:11])=[C:8]([F:12])[CH:7]=3)[C:4](=[O:17])[NH:20][C:21]2=[O:22])[CH2:15][CH2:16]1

참가 물질

4

반응물 2

HCID 21979164Chlorosulfanyl isocyanateHCID 690700502-Cyclopropylamino-4,5-difluorobenzoic acid ethyl ester

생성물 1

HCID 112764481-Cyclopropyl-6,7-difluoroquinazoline-2,4(1H,3H)-dione수율 38.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
-20 °C

실험 절차

To a solution of 2-cyclopropylamino-4,5-difluorobenzoic acid ethyl ester (Example 22) (5.0 g, 22.0 mmol) in dry dichloromethane (120 mL) under a N2 atmosphere is added chlorosulfanyl isocyanate (3.11 g, 22 mmol). The solution is reacted at room temperature for 4 hours, and the solvent is removed under reduced pressure. The residue is cooled to −20° C., and a cold brine solution (100 mL) buffered with NaHCO3 is added. The solution is warmed to room temperature for 1 hour. The volume is reduced by half with a stream of air, and the solid is collected by filtration. The dry solid is added to a solution of triethylamine (5 mL) in THF (250 mL) and refluxed overnight. The reaction is cooled, the solvent removed under reduced pressure, dissolved in water (100 mL), and acidified to pH 1–2 with 1.0 M hydrochloric acid. The resulting precipitate is collected via filtration to afford 2.0 g of the title compound. MS CI: m/z 239 (MH+).

후처리

  1. customThe solution is reacted at room temperature for 4 hours
  2. customthe solvent is removed under reduced pressure
  3. additionis added
  4. temperatureThe solution is warmed to room temperature for 1 hour
  5. filtrationthe solid is collected by filtration
  6. additionThe dry solid is added to a solution of triethylamine (5 mL) in THF (250 mL)
  7. temperaturerefluxed overnight
  8. temperatureThe reaction is cooled
  9. customthe solvent removed under reduced pressure
  10. dissolutiondissolved in water (100 mL)
  11. filtrationThe resulting precipitate is collected via filtration

출처 및 근거

ORD 기록
ord-bf2e5b26c85a4325b8e0f4a034dc0c42
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094780B1

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