Diethyl chlorophosphate → 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-acetylaminobutyrate

HRID 1029508노트

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HRID 1029508 반응식
[H-].[Na+].[OH:3][CH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]1[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[N:17][C:18]([O:24][CH3:25])=[CH:19][CH:20]=2)[N:15]=1.P(Cl)(OCC)(OCC)=O.[C:35]([NH:38][CH2:39][CH2:40][CH2:41][C:42]([O-])=[O:43])(=[O:37])[CH3:36].[Na+].C(NCCCC(O)=O)(=O)C>CN(C)C=O.O>[C:35]([NH:38][CH2:39][CH2:40][CH2:41][C:42]([O:13][CH:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4](=[O:3])[N:5]1[C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[N:17][C:18]([O:24][CH3:25])=[CH:19][CH:20]=2)[N:15]=1)=[O:43])(=[O:37])[CH3:36]

참가 물질

8

반응물 5

HCID 13139Diethyl chlorophosphateHCID 181894-Acetamidobutyric acidHCID 24758Sodium hydride2회HCID 141821812-(7-Methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-1-isoindolinoneHCID 23690616Sodium 4-acetylaminobutanoate

생성물 1

HCID 700577042-(7-Methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-acetylaminobutyrate

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

An oily suspension (50% by weight; 0.96 g) of sodium hydride is added in the course of 15 minutes to a suspension of 3-hydroxy-2-(7-methoxy-1,8-naphthyridin-2-yl)-1-isoindolinone (6.15 g) in anhydrous dimethylformamide (50 cc) while the temperature is maintained in the region of 0° C., the mixture then being stirred again for 30 minutes at 0° C. Diethyl chlorophosphate (2.9 cc) is then added dropwise in the course of 30 minutes while the temperature is maintained in the region of 0° C. A solution of sodium 4-acetylaminobutanoate, prepared from 4-acetamidobutyric acid (2.9 g) in anhydrous dimethylformamide (30 cc) and an oily suspension (50% by weight; 0.96 g) of sodium hydride, is added at a temperature in the region of 0° C. to the solution obtained. The mixture is stirred for 1 hour at 0° C., then 20 hours at a temperature in the region of 20° C., and finally 4 hours at 80° C. The reaction mixture is poured into water (400 cc) and extracted with methylene chloride (3×200 cc). The organic extracts are combined and washed with water, dried and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is purified by chromatography on silica (0.063-0.2 mm; 350 g) contained in a column 5 cm in diameter [eluant: methylene chloride/methanol (99:1 by volume)], collecting 100-cc fractions. Fractions 23 to 39 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C.; the residue is recrystallized in acetonitrile. 2-(7-Methoxy-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-acetylaminobutyrate (2 g), m.p. 190° C., is thereby obtained.

후처리

  1. temperatureis maintained in the region of 0° C
  2. customobtained
  3. stirringThe mixture is stirred for 1 hour at 0° C.
  4. custom20 hours
  5. customin the region of 20° C., and finally 4 hours
  6. customat 80° C
  7. extractionextracted with methylene chloride (3×200 cc)
  8. washwashed with water
  9. customdried
  10. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  11. customThe residue obtained
  12. customis purified by chromatography on silica (0.063-0.2 mm; 350 g)
  13. customcollecting 100-cc fractions
  14. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C.
  15. customthe residue is recrystallized in acetonitrile

출처 및 근거

ORD 기록
ord-4d9772e406044c819c9c7fc5ef465586
출처 데이터셋
uspto-grants-1992_04
특허 번호
US05102890

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