Isatin → 3-Methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione

HRID 34548

반응식

HRID 34548 반응식
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[CH3:12][N:13]=[C:14]=[O:15].C[NH:17][C:18]([N:20]1C2C(=CC=CC=2)C(=O)C1=O)=[O:19].Br.C(SC(=N)N)C>O1CCCC1.C(N(CC)CC)C>[CH3:12][N:13]1[C:4]2([C:2](=[O:3])[NH:20][C:18](=[O:19])[NH:17]2)[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[NH:1][C:14]1=[O:15]

참가 물질

7

반응물 4

HCID 7054IsatinHCID 12228Methyl IsocyanateHCID 200213S-Ethylisothiuronium bromideHCID 2835543N-(methylcarbamoyl)isatin

생성물 1

HCID 142299883-Methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione수율 75%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매2회

반응 조건

온도
70 °C

실험 절차

Isatin (294.3 g) is suspended in tetrahydrofuran (3 liter) and thereto are added with stirring triethylamine (279 ml) and methyl isocyanate (129.8 ml) at 15° C. The mixture is stirred at 20°-25° C. for 2.5 hours (1-methylcarbamoylisatin is produced in the mixture). To the reaction mixture are added 2-ethylisothiourea hydrobromide (444.2 g) and triethylamine (55.8 ml), and the mixture is refluxed for 2 hours. After cooling, the solvent is distilled off under reduced pressure. To the residue [i.e. 3-methyl-4-hydroxy-4-(2-ethylisothioureido)carbonyl-2-oxo1,2,3,4-tetrahydroquinazoline] is added 10% hydrochloric acid (4 liter) and the mixture is stirred at 70° C. for 4 hours. After cooling, the precipitates are taken by filtration, washed with water, methanol (1 liter) and chloroform (1 liter) in this order and then dried to give 3-methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione (369.2 g, yield 75 %).

후처리

  1. customis produced in the mixture)
  2. temperaturethe mixture is refluxed for 2 hours
  3. temperatureAfter cooling
  4. distillationthe solvent is distilled off under reduced pressure
  5. additionTo the residue [i.e. 3-methyl-4-hydroxy-4-(2-ethylisothioureido)carbonyl-2-oxo1,2,3,4-tetrahydroquinazoline] is added 10% hydrochloric acid (4 liter)
  6. temperatureAfter cooling
  7. filtrationthe precipitates are taken by filtration
  8. washwashed with water, methanol (1 liter) and chloroform (1 liter) in this order
  9. customdried

출처 및 근거

ORD 기록
ord-5590a2d8fe894688ad10925b9cbadf48
출처 데이터셋
uspto-grants-1988_08
특허 번호
US04762839

연결된 노트

불러오는 중…