Oxalic Acid → 2-(7-Bromo-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one

HRID 259645

反応式

HRID 259645 の反応式
[Br:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:20]([OH:21])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:26]([N:28]1[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]1)=[O:27].C(O)(=O)C(O)=O.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(O)C.C(Cl)Cl>[Br:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[CH:20]([O:21][C:26]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)=[O:27])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])=[N:9]2)=[CH:4][CH:3]=1

参加物

9

反応物 5

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 30169354-Methyl-1-piperazinecarbonyl chlorideHCID 199004212-(7-Bromo-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinone

生成物 1

HCID 214220682-(7-Bromo-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one収率 8.3%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒2 回HCID 6228Dimethylformamide溶媒2 回HCID 6344Dichloromethane溶媒

反応条件

温度
26 °C

実験手順

The procedure described in Example 4 is followed but starting with 2-(7-bromo-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (8 g.) in anhydrous dimethylformamide (240 cc.), sodium hydride (50% dispersion in mineral oil) (1.2 g.) and 1-chlorocarbonyl-4-methylpiperazine (4.1 g.) in anhydrous dimethylformamide (40 cc.). After stirring at 26° C. for 18 hours, the reaction mixture is poured into ice-water (1,500 cc.). The insoluble matter (7.3 g.) is filtered off and dissolved in a mixture (73 cc.) of methylene chloride and ethyl acetate (80-20 by volume). The solution obtained is passed through a column of silica gel (73 g.). Elution is first carried out with a mixture (5,750 cc.) of methylene chloride and ethyl acetate (80-20 by volume); the corresponding eluates are discarded. Elution is then carried out with pure ethyl acetate (1,250 cc.) and then with a mixture (1,250 cc.) of ethyl acetate and methanol (50--50 by volume); the corresponding eluates are combined and concentrated to dryness. A residue (3 g.) is obtained which is dissolved in ethanol (90 cc.). A solution of oxalic acid (0.53 g.) in ethanol (10.5 cc.) is added to the solution obtained. The mixture is stirred for 1 hour and the precipitate which forms is filtered off and washed with ethanol (6 cc.). A product (1.8 g.), melting at 260° C., is thus obtained and is treated with a saturated solution of sodium bicarbonate (50 cc.) and methylene chloride (40 cc.). The organic layer is isolated by decanting, dried over anhydrous potassium carbonate and concentrated to dryness. A residue weighing 1.2 g. is obtained and is recrystallised from ethanol (80 cc.). 2-(7-Bromo-1,8-naphthyridin-2-yl)-3-(4-methylpiperazin-1yl)carbonyloxy-isoindolin-1-one (0.9 g.), melting at 225°-230° C., is thus obtained.

後処理

  1. filtrationThe insoluble matter (7.3 g.) is filtered off
  2. dissolutiondissolved in a mixture (73 cc.) of methylene chloride and ethyl acetate (80-20 by volume)
  3. customThe solution obtained
  4. washElution
  5. washElution
  6. concentrationconcentrated to dryness
  7. customA residue (3 g.) is obtained which
  8. customobtained
  9. stirringThe mixture is stirred for 1 hour
  10. filtrationthe precipitate which forms is filtered off
  11. washwashed with ethanol (6 cc.)
  12. customA product (1.8 g.), melting at 260° C., is thus obtained
  13. customThe organic layer is isolated
  14. customby decanting
  15. dry with materialdried over anhydrous potassium carbonate
  16. concentrationconcentrated to dryness
  17. customis obtained
  18. customis recrystallised from ethanol (80 cc.)

出典と根拠

ORDレコード
ord-f6ede0c4444047c1b7f684677621cdb4
出典データセット
uspto-grants-1977_07
特許番号
US04038391

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