Hexamethylphosphoramide → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one

HRID 259644

반응식

HRID 259644 반응식
[H-].[Na+].[CH3:3][O:4][C:5]1[N:14]=[C:13]2[C:8]([CH:9]=[CH:10][C:11]([N:15]3[CH:23]([OH:24])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16]3=[O:25])=[N:12]2)=[CH:7][CH:6]=1.Cl[C:27]([N:29]1[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]1)=[O:28].CN(P(N(C)C)(N(C)C)=O)C>CN(C)C=O>[CH3:3][O:4][C:5]1[N:14]=[C:13]2[C:8]([CH:9]=[CH:10][C:11]([N:15]3[CH:23]([O:24][C:27]([N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)=[O:28])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:16]3=[O:25])=[N:12]2)=[CH:7][CH:6]=1

참가 물질

6

반응물 4

HCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 30169354-Methyl-1-piperazinecarbonyl chlorideHCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

생성물 1

HCID 214221092-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one수율 45.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

Sodium hydride (50% dispersion in mineral oil) (0.8 g.) is added to a suspension of 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (4.63 g.) in anhydrous dimethylformamide (45 cc.), whilst keeping the temperature between 18°-20° C. The reaction mixture is stirred for a further 4 hours 30 minutes. A solution of 1-chlorocarbonyl-4-methylpiperazine (2.7 g.) in anhydrous dimethylformamide (25 cc.) is then added over the course of 15 minutes and at a temperature of 20° C. The suspension is stirred for 17 hours at a temperature of about 20° C., and then anhydrous hexamethylphosphotriamide (7 cc.) is added. After 15 minutes, the reaction mixture is poured into ice-water (500 g.). The precipitate is filtered off and washed with water (45 cc.). A product (6.1 g.) is obtained and is recrystallised from diisopropyl ether (1,500 cc.). 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-(4 -methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one (3 g.), melting at 191° C., is thus obtained.

후처리

  1. custombetween 18°-20° C
  2. stirringThe suspension is stirred for 17 hours at a temperature of about 20° C.
  3. waitAfter 15 minutes
  4. filtrationThe precipitate is filtered off
  5. washwashed with water (45 cc.)
  6. customA product (6.1 g.) is obtained
  7. customis recrystallised from diisopropyl ether (1,500 cc.)

출처 및 근거

ORD 기록
ord-f6d9a6c5b14e4618a54b3b7e9798e706
출처 데이터셋
uspto-grants-1977_07
특허 번호
US04038391

연결된 노트

불러오는 중…