Potassium Carbonate → 6-chloro-7-(3-cyanophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide

HRID 589856Notes

Reaction equation

HRID 589856 reaction equation
[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][NH:9][CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[N:21])[CH:15]=1.[O:22]1[CH2:27][CH2:26][CH:25]([NH:28][C:29](=O)[O:30]C2C=CC([N+]([O-])=O)=CC=2)[CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:29]([NH:28][CH:25]3[CH2:26][CH2:27][O:22][CH2:23][CH2:24]3)=[O:30])[CH2:10][C:5]2=[C:4]([C:11]([NH2:13])=[O:12])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]#[N:21])[CH:15]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 665843044-nitrophenyl tetrahydro-2H-pyran-4-ylcarbamateHCID 665846626-Chloro-7-(3-cyanophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide

Product 1

HCID 665851046-chloro-7-(3-cyanophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamideYield 82.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 0.67 g (2.23 mmol) of 6-chloro-7-(3-cyanophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxamide, 0.712 g (2.67 mmol) of 4-nitrophenyl tetrahydro-2H-pyran-4-ylcarbamate and 0.616 g (1.12 mmol) of potassium carbonate in 10 ml of acetonitrile is heated at 65° C. for 1 hour 30 minutes. After cooling, the mixture is concentrated under reduced pressure, the residue is diluted with dichloromethane and the solution is washed with aqueous 1N sodium hydroxide solution. The organic phase is washed with water, dried over sodium sulfate and filtered, and the solvent is evaporated off under reduced pressure. The residue is purified by chromatography on a column of 40 g of silica gel, eluting with a mixture of 2 to 5% methanol in dichloromethane, to give 0.79 g of 6-chloro-7-(3-cyanophenyl)-N2-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide in the form of a whitish powder after recrystallizing from 100 ml of ethanol, filtering off and drying under reduced pressure.

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture is concentrated under reduced pressure
  3. additionthe residue is diluted with dichloromethane
  4. washthe solution is washed with aqueous 1N sodium hydroxide solution
  5. washThe organic phase is washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent is evaporated off under reduced pressure
  9. customThe residue is purified by chromatography on a column of 40 g of silica gel
  10. washeluting with a mixture of 2 to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-0af065888b3142398b3394629aaecca7
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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