Triethylamine → 6-(7-chloro-1,8-naphthyridin-2-yl)-5-cyclohexylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine

HRID 66349Notes

Reaction equation

HRID 66349 reaction equation
[CH:1]1([N:7]=[C:8]=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:10][C:11]1[N:20]=[C:19]2[C:14]([CH:15]=[CH:16][C:17]([N:21]3[CH:29]([OH:30])[C:28]4[C:23](=[N:24][CH:25]=[CH:26][N:27]=4)[C:22]3=[O:31])=[N:18]2)=[CH:13][CH:12]=1.C(N(CC)CC)C.[OH-].[Na+]>C(#N)C.C(O)C>[Cl:10][C:11]1[N:20]=[C:19]2[C:14]([CH:15]=[CH:16][C:17]([N:21]3[CH:29]([O:30][C:8]([NH:7][CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[O:9])[C:28]4[C:23](=[N:24][CH:25]=[CH:26][N:27]=4)[C:22]3=[O:31])=[N:18]2)=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 18502Cyclohexyl isocyanateHCID 64531286-(7-chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one

Product 1

HCID 227547626-(7-chloro-1,8-naphthyridin-2-yl)-5-cyclohexylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazineYield 41.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

Cyclohexyl isocyanate (1.38 g.) is added to a suspension of 6-(7-chloro-1,8-naphthyridin-2-yl)-5-hydroxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (3.12 g.) in anhydrous acetonitrile (60 cc.) in the presence of triethylamine (1 cc.), and the reaction mixture is heated at the reflux temperature for 13 hours. After cooling, the insoluble product is filtered off and washed successively with acetonitrile (2 × 10 cc.) and diisopropyl ether (2 × 20 cc.). It is then dissolved in methylene chloride (300 cc.) and the solution obtained is stirred for 15 minutes with 1N sodium hydroxide solution (50 cc.). The organic layer is decanted, washed with water (2 × 50 cc.), dried over anhydrous sodium sulphate in the presence of decolourising charcoal, filtered and then evaporated to dryness under reduced pressure. The residue is recrystallised from acetonitrile (95 cc.) and the product obtained is heated for 10 minutes with ethanol (65 cc.) at the reflux temperature. The insoluble product is then isolated from the boiling solution by filtration, after which it is washed with boiling ethanol (2 × 10 cc.). After drying, 6-(7-chloro-1,8-naphthyridin-2-yl)-5-cyclohexylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (1.8 g.), melting at 264° C., is obtained.

Workup

  1. temperaturethe reaction mixture is heated at the reflux temperature for 13 hours
  2. temperatureAfter cooling
  3. filtrationthe insoluble product is filtered off
  4. washwashed successively with acetonitrile (2 × 10 cc.) and diisopropyl ether (2 × 20 cc.)
  5. dissolutionIt is then dissolved in methylene chloride (300 cc.)
  6. customthe solution obtained
  7. customThe organic layer is decanted
  8. washwashed with water (2 × 50 cc.)
  9. dry with materialdried over anhydrous sodium sulphate in the presence of decolourising charcoal
  10. filtrationfiltered
  11. customevaporated to dryness under reduced pressure
  12. customThe residue is recrystallised from acetonitrile (95 cc.)
  13. customthe product obtained
  14. customThe insoluble product is then isolated from the boiling solution by filtration
  15. washafter which it is washed with boiling ethanol (2 × 10 cc.)
  16. customAfter drying

Sources & evidence

ORD record
ord-8bf04ef0911e42cb9ce241a8161b6eb3
Source dataset
uspto-grants-1978_12
Patent number
US04131674

Reaction notes

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