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

HRID 259644

Reaction equation

HRID 259644 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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.)

Sources & evidence

ORD record
ord-f6d9a6c5b14e4618a54b3b7e9798e706
Source dataset
uspto-grants-1977_07
Patent number
US04038391

Linked notes

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