Sodium Carbonate → HCID 58382356, compound

HRID 1969791Notes

Reaction equation

HRID 1969791 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)[N:5]2[C:10]3[CH:11]=[CH:12][N:13](S(C4C=CC(C)=CC=4)(=O)=O)[C:9]=3[N:8]=[CH:7][C:6]=12.[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O.CCOC(C)=O.[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH:24]1([C:4]2[N:5]3[C:10]4[CH:11]=[CH:12][NH:13][C:9]=4[N:8]=[CH:7][C:6]3=[C:2]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:3]=2)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 583822553-Bromo-1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine

Product 1

HCID 58382356HCID 58382356, compoundYield 28.2%

Reagents, catalysts & solvents 5

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-bromo-1-cyclohexyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.27 g, 0.056 mmol, Preparation #MM.1) and PdCl2(dppf)•DCM adduct (0.0046 g, 0.0056 mmol) in THF (1 mL) was added a solution of phenylboronic acid (0.12 g, 0.098 mmol) and Na2CO3 (0.009 g, 0.084 mmol) in water (0.25 mL). The reaction mixture was heated to about 60° C. After about 6 h, the reaction mixture was cooled to ambient temperature and was diluted with EtOAc (5 mL) and brine (5 mL). The organic layer was separated and concd in vacuo. The residue was dissolved in 1,4-dioxane (5 mL) and NaOH (2 N aqueous, 1 mL) was added. The reaction mixture was heated to about 65° C. After about 15 h, the reaction mixture was cooled to ambient temperature and HCl (1 N aqueous, 3 mL) and EtOAc (5 mL) were added. The organic layer was separated, concd in vacuo, and the residue was purified by chromatography on silica gel (12 g) eluting with 20-80% EtOAc in DCM to provide 1-cyclohexyl-3-phenyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.005 g, 28%) as a solid: LC/MS (Table 1, Method a) Rt=2.75 min; MS m/z: 317 (M+H)+.

Workup

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. customThe organic layer was separated
  3. dissolutionThe residue was dissolved in 1,4-dioxane (5 mL)
  4. additionNaOH (2 N aqueous, 1 mL) was added
  5. temperatureThe reaction mixture was heated to about 65° C
  6. waitAfter about 15 h
  7. temperaturethe reaction mixture was cooled to ambient temperature
  8. additionHCl (1 N aqueous, 3 mL) and EtOAc (5 mL) were added
  9. customThe organic layer was separated
  10. customconcd in vacuo, and the residue was purified by chromatography on silica gel (12 g)
  11. washeluting with 20-80% EtOAc in DCM

Sources & evidence

ORD record
ord-9be8578a8b2f4b92896363078b73dfa2
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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