Dimethylformamide → HCID 71248772, compound

HRID 1019825Notes

Reaction equation

HRID 1019825 reaction equation
Br[C:2]1[N:6]2[C@@H:7]([CH3:15])[CH2:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:11])[C:5]2=[C:4]([O:16][CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].N.O.[CH3:25][N:26](C)C=O>>[C:25]([C:2]1[N:6]2[C@@H:7]([CH3:15])[CH2:8][N:9]([CH:12]([CH3:14])[CH3:13])[C:10](=[O:11])[C:5]2=[C:4]([O:16][CH3:17])[C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:26]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 12896473Azane;hydrateHCID 86676512HCID 86676512, compound

Product 1

HCID 71248772HCID 71248772, compoundYield 80%

Conditions

Temperature
110 °C

Procedure

(S)-ethyl 6-bromo-2-isopropyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydro-pyrrolo[1,2-a]pyrazine-7-carboxylate (1.2 mol) and Cu(I)CN (2.4 mol) were dissolved in dimethylformamide (DMF; 2.2 l) at 20° C. under N2. The mixture was stirred for 2 h at 110° C. Concentrated NH3.H2O (650 ml) was added at 60° C. The mixture was stirred for 30 min at 60° C. and then cooled to 20° C. The mixture was filtered off. Ethyl acetate (3000 ml) and H2O (2000 ml) were added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3×1000 ml). The combined organic layers were washed with brine, dried and concentrated in vacuo. The crude product and a small batch of an earlier preparation were combined and washed with methyl tert-butyl ether to give a solid. Yield: 350 g of Intermediate I-3 (95% purity, 80% yield total).

Workup

  1. stirringThe mixture was stirred for 30 min at 60° C.
  2. temperaturecooled to 20° C
  3. filtrationThe mixture was filtered off
  4. additionEthyl acetate (3000 ml) and H2O (2000 ml) were added
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was extracted with ethyl acetate (3×1000 ml)
  7. washThe combined organic layers were washed with brine
  8. customdried
  9. concentrationconcentrated in vacuo
  10. customThe crude product and a small batch of an earlier preparation
  11. washwashed with methyl tert-butyl ether
  12. customto give a solid

Sources & evidence

ORD record
ord-0faedba309b54db09456dbe3d84a86ca
Source dataset
uspto-grants-2014_05
Patent number
US08716293B2

Reaction notes

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