Tetrahydrofuran → HCID 70638456, compound

HRID 259648Notes

Reaction equation

HRID 259648 reaction equation
[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[C:20](=[O:21])[C:19]4[C:14](=[N:15][CH:16]=[CH:17][CH:18]=4)[CH:13]3[OH:22])=[N:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[N:26]1[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][C:27]1=C=O.[O:35]1CCC[CH2:36]1>>[CH3:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([N:12]3[C:20](=[O:21])[C:19]4[C:14](=[N:15][CH:16]=[CH:17][CH:18]=4)[CH:13]3[O:22][C:36]([N:26]3[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]3)=[O:35])=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 70638029HCID 70638029, compoundHCID 86734973HCID 86734973, compound

Product 1

HCID 70638456HCID 70638456, compound

Procedure

Following the procedure of Example 9 but starting with a suspension of 6-(7-methyl-1,8-naphthyridin-2-yl)-7-hydroxy-5-oxo-pyrrolo[3,4-b]pyridine (2.7 g.) in anhydrous tetrahydrofuran (27 cc.), sodium hydride (50% dispersion in mineral oil) (0.885 g.) and 1chloro-carbonyl-4-methylpiperazine (3 g.) dissolved in anhydrous tetrahydrofuran (30 cc.), a reaction mixture is obtained which is poured into ice-water (210 cc.). The mixture is extracted with methylene chloride (3 × 400 cc.). The combined extracts are dried over potassium carbonate and are concentrated to dryness. A residue weighing 4.9 g. is thus obtained and is triturated with diisopropyl ether (60 cc.). The precipitate which appears is filtered off. The resulting product (3.6 g.) is dissolved in methylene chloride (72 cc.), and the solution is passed through a column of silica gel (36 g.). Elution is carried out successively with methylene chloride (3 × 500 cc.), a mixture (3 × 500 cc.) of methylene chloride and ethyl acetate (50--50 by volume), pure ethyl acetate (3 × 500 cc.) and a mixture (4 × 500 cc.) of ethyl acetate and methanol (90-10 by volume). The last four eluates are concentrated to dryness and the residue obtained is recrystallised from acetonitrile (58 cc.). 6-(7-Methyl-1,8-naphthyridin-2-yl)-7-(4-methylpiperazin-1-yl)carbonyloxy-5-oxo-pyrrolo[3,4-b]pyridine (1.12 g.), melting at 226° C., is thus obtained.

Workup

  1. customa reaction mixture is obtained which
  2. extractionThe mixture is extracted with methylene chloride (3 × 400 cc.)
  3. dry with materialThe combined extracts are dried over potassium carbonate
  4. concentrationare concentrated to dryness
  5. customis thus obtained
  6. customis triturated with diisopropyl ether (60 cc.)
  7. filtrationThe precipitate which appears is filtered off
  8. dissolutionThe resulting product (3.6 g.) is dissolved in methylene chloride (72 cc.)
  9. washElution
  10. concentrationThe last four eluates are concentrated to dryness
  11. customthe residue obtained
  12. customis recrystallised from acetonitrile (58 cc.)

Sources & evidence

ORD record
ord-6bdf317c4c53475cb6d9e05c68f3b1b9
Source dataset
uspto-grants-1977_07
Patent number
US04038391

Reaction notes

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