Dichloromethane → HCID 58382356, compound

HRID 1628108Notes

Reaction equation

HRID 1628108 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(Cl)Cl.[C:33]1(B(O)O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=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]>[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:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:3]=2)[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 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 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 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) and PdCl2(dppf).DCM (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 mixture was heated to about 60° C. After about 6 h, the mixture was cooled to rt and was diluted with EtOAc (5 mL) and brine (5 mL). The organic layer was separated and concentrated in vacuo. The residue was dissolved in 1,4-dioxane (5 mL) and aqueous NaOH (2 N, 1 mL) was added. The mixture was heated to about 65° C. After about 15 h, the mixture was cooled to rt and aqueous HCl (1 N, 3 mL) and EtOAc (5 mL) were added. The organic layer was separated, concentrated in vacuo, and the residue was purified by chromatography on silica gel (12 g) eluting with 20 to 80% EtOAc in DCM to provide 1-cyclohexyl-3-phenyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazine (0.005 g, 28%): LC/MS (Table 2, Method a) Rf=2.75 min; MS m/z: 317 (M+H)+. Syk IC50=C.

Workup

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

Sources & evidence

ORD record
ord-722de99ec71c4cd0a62956f62344ffbc
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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