Dichloromethane → 6-(7-Chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-oxo-5H-pyrrole(3,4-b)pyrazin-5-yl dimethylcarbamate

HRID 66339Notes

Reaction equation

HRID 66339 reaction equation
[CH3:1][N:2]([CH3:6])[C:3](Cl)=[O:4].C(N(CC)CC)C.[Cl:14][C:15]1[N:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21]([N:25]3[CH:33]([OH:34])[C:32]4[C:27](=[N:28][CH:29]=[CH:30][N:31]=4)[C:26]3=[O:35])=[N:22]2)=[CH:17][CH:16]=1.C(Cl)Cl>C(#N)C.CN(C)C=O.O.N1C=CC=CC=1>[Cl:14][C:15]1[N:24]=[C:23]2[C:18]([CH:19]=[CH:20][C:21]([N:25]3[CH:33]([O:34][C:3]([N:2]([CH3:6])[CH3:1])=[O:4])[C:32]4[C:27](=[N:28][CH:29]=[CH:30][N:31]=4)[C:26]3=[O:35])=[N:22]2)=[CH:17][CH:16]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 64531286-(7-chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one

Product 1

HCID 227547576-(7-Chloro-1,8-naphthyridin-2-yl)-6,7-dihydro-7-oxo-5H-pyrrole(3,4-b)pyrazin-5-yl dimethylcarbamateYield 62.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Dimethylcarbamoyl chloride (4.85 g.) and triethylamine (4.55 g.) are added successively 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 (4.7 g.) in a mixture of anhydrous methylene chloride (47 cc.) and anhydrous pyridine (16 cc.). The reaction mixture is heated at the reflux temperature for 2 hours, and is then cooled and poured into water (180 cc.). A slight amount of insoluble matter is filtered off and the aqueous layer is decanted off and washed with methylene chloride (2 × 50 cc.) by successive decantations. The combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 33 cc.), dried with anhydrous sodium sulphate in the presence of decolourising charcoal, filtered and evaporated to dryness under reduced pressure. The residue obtained is taken up in acetonitrile (20 cc.) and the insoluble product is filtered off and washed with acetonitrile (3 × 2 cc.). Recrystallisation of this product from dimethylformamide (14 cc.) gives a solvated product (4.1 g.). This product is dissolved in dimethylformamide (100 cc.) at a temperature of about 70° C. The solution thus obtained is poured into water (1,200 cc.) and the insoluble product is filtered off and washed with water (5 × 20 cc.). After drying, 6-(7-chloro-1,8-naphthyridin-2-yl)-5-dimethylaminocarbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine (3.6 g.), melting at 270° C., is obtained.

Workup

  1. temperatureThe reaction mixture is heated at the reflux temperature for 2 hours
  2. temperatureis then cooled
  3. filtrationA slight amount of insoluble matter is filtered off
  4. customthe aqueous layer is decanted off
  5. washwashed with methylene chloride (2 × 50 cc.) by successive decantations
  6. washThe combined organic layers are washed by successive decantations with 1N sodium hydroxide solution (2 × 30 cc.) and water (2 × 33 cc.)
  7. dry with materialdried with anhydrous sodium sulphate in the presence of decolourising charcoal
  8. filtrationfiltered
  9. customevaporated to dryness under reduced pressure
  10. customThe residue obtained
  11. filtrationthe insoluble product is filtered off
  12. washwashed with acetonitrile (3 × 2 cc.)
  13. customRecrystallisation of this product from dimethylformamide (14 cc.)
  14. customgives a solvated product (4.1 g.)
  15. customThe solution thus obtained
  16. filtrationthe insoluble product is filtered off
  17. washwashed with water (5 × 20 cc.)
  18. customAfter drying

Sources & evidence

ORD record
ord-9a3b6c1266164486843ea24d1d38d68f
Source dataset
uspto-grants-1978_12
Patent number
US04131674

Reaction notes

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