Sodium Iodide → (3RS)-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one

HRID 963469노트

반응식

HRID 963469 반응식
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH:11]1[N:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C:15]2[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=2[NH:13][C:12]1=[O:29])=[O:9])([CH3:6])([CH3:5])[CH3:4].[I-].[Na+].Cl[CH2:33][C:34]([N:36]1[CH2:44][CH:43]2[CH2:45][CH:39]3[CH2:40][CH:41]([CH2:46][CH:37]1[CH2:38]3)[CH2:42]2)=[O:35]>CN(C)C=O>[CH:37]12[CH2:46][CH:41]3[CH2:40][CH:39]([CH2:45][CH:43]([CH2:42]3)[CH2:44][N:36]1[C:34]([CH2:33][N:13]1[C:14]3[CH:28]=[CH:27][CH:26]=[CH:25][C:15]=3[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])=[N:17][CH:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[C:12]1=[O:29])=[O:35])[CH2:38]2

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 19081122(3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-oneHCID 86752745N-chloromethylcarbonyl-2-azatricyclo-[4.3.1.14,8]undecane

생성물 1

HCID 67688125(3RS)-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one수율 120.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

실험 절차

To a suspension of sodium hydride (0.035 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (5 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.293 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooling in an ice-bath. After completion of the addition, the mixture was allowed to stand to room temperature and stirred for 2 hours. To the the mixture was added sodium iodide (0.129 g) and followed dropwise a solution of N-chloromethylcarbonyl-2-azatricyclo-[4.3.1.14,8 ]undecane (0.215 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooing in an ice-bath for 1 hour and then at room temperature overnight. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer was washed with water and dried over sodium sulfate. Removal of the solvent gave (3RS)-1-[(2-azatricyclo[4.3.1.14,8 ]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.537 g), which was used in a following reaction step without further purification.

후처리

  1. temperatureat cooling in an ice-bath
  2. additionAfter completion of the addition
  3. customto stand to room temperature
  4. stirringstirred for 2 hours
  5. stirringunder stirring
  6. customat room temperature
  7. customovernight
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. additionThe residue was treated with ethyl acetate and water
  10. washThe organic layer was washed with water
  11. dry with materialdried over sodium sulfate
  12. customRemoval of the solvent

출처 및 근거

ORD 기록
ord-d74e1b54a58d423c9c303dbf423343b6
출처 데이터셋
uspto-grants-1998_06
특허 번호
US05763437

반응 노트

불러오는 중…