Water → HCID 68593675, compound

HRID 220438Notes

Reaction equation

HRID 220438 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([Cl:20])=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].[CH3:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=1B(O)O.O>CN(C)C(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:20].[ClH:20].[CH3:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=1[C:19]1[C:14]([N:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[N:15][CH:16]=[CH:17][N:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 5833222,6-Dimethylphenylboronic acidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 68593675HCID 68593675, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

Dissolve 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (1.00 g, 3.35 mmol) in N,N-dimethylacetamide (purged with nitrogen) (12 mL). Add potassium carbonate (1.11 g, 8.04 mmol) then 2,6-dimethylbenzeneboronic acid (602 mg, 4.02 mmol) and purge with nitrogen for 10 min. Add deoxygenated water (6 mL) and tetrakis(triphenylphosphine)palladium(0) (0.039 g, 0.034 mmol) and purge with nitrogen for 10 min. Heat at 115° C. for 20 hr. under nitrogen. Cool to room temperature, add water (20 mL), extract with DCM (3×20 mL) and pass through an IST Phase Separator Frit® and concentrate. Dissolve in methanol, filter off solid and purify filtrate by SCX-2® chromatography washing with methanol then eluting with 2 M ammonia in methanol. Concentrate, then stir in HCl in dioxane (4 M, 50 mL) for 3 hr. at room temperature. Reduce solvent, add potassium carbonate (2 g), filter and concentrate filtrate. Purify by SCX-2® chromatography, washing with methanol then eluting with 4 M ammonia in methanol, and concentrate. Add HCl in diethyl ether (1 M, 20 mL) and concentrate, then dry under vacuum at 40° C. to give the title preparation as yellow crystals (650 mg, 57%). MS (ES): m/z=269 [M+H]+.

Workup

  1. additionAdd
  2. custompurge with nitrogen for 10 min
  3. temperatureCool to room temperature
  4. additionadd water (20 mL)
  5. extractionextract with DCM (3×20 mL)
  6. concentrationconcentrate
  7. dissolutionDissolve in methanol
  8. filtrationfilter off solid
  9. custompurify filtrate by SCX-2® chromatography
  10. washwashing with methanol
  11. washthen eluting with 2 M ammonia in methanol
  12. concentrationConcentrate
  13. customat room temperature
  14. additionReduce solvent, add potassium carbonate (2 g)
  15. filtrationfilter
  16. concentrationconcentrate filtrate
  17. customPurify by SCX-2® chromatography
  18. washwashing with methanol
  19. washthen eluting with 4 M ammonia in methanol
  20. concentrationconcentrate
  21. concentrationAdd HCl in diethyl ether (1 M, 20 mL) and concentrate
  22. customdry under vacuum at 40° C.
  23. customto give the title

Sources & evidence

ORD record
ord-e1da5fc2ff26423d82d375df4d169ff6
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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