Nitrogen → 6-Methyl-2,3-di-p-tolyl-5H-pyrrolo[2,3-b]pyrazine

HRID 1428675Notes

Reaction equation

HRID 1428675 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:11]=[C:10]([CH3:12])[NH:9][C:5]2=[N:6][C:7]=1Cl.N#N.B(O)(O)[C:16]1[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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>[CH3:12][C:10]1[NH:9][C:5]2=[N:6][C:7]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)=[C:2]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)[N:3]=[C:4]2[CH:11]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 79799Tolylboronic acid2×HCID 866903242-Bromo-3-chloro-6-methyl-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 866903256-Methyl-2,3-di-p-tolyl-5H-pyrrolo[2,3-b]pyrazine

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

2-Bromo-3-chloro-6-methyl-5H-pyrrolo[2,3-b]pyrazine (step 3) (183 mg, 0.742 mmol) in dioxane (5 ml) was degassed with N2 and treated with p-tolylboronic acid (242 mg, 1.782 mmol), K2CO3 (308 mg, 2.227 mmol) and PdCl2(dppf)-CH2Cl2-adduct (60.6 mg, 0.074 mmol). The reaction mixture was heated at reflux for 3 hours. After cooling to RT, further portions of p-tolyl boronic acid (242 mg, 1.782 mmol) and PdCl2(dppf)-CH2Cl2-adduct (60.6 mg, 0.074 mmol) were added and heating continued at reflux for 2 hours. After cooling to RT, the mixture was diluted with water (50 ml). The resultant suspension was sonicated and filtered, rinsing the filter cake with water (×3). Purification of the crude product by chromatography on silica eluting with 0-30% EtOAc in iso-hexane afforded the titled compound;

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureheating
  4. temperatureat reflux for 2 hours
  5. temperatureAfter cooling to RT
  6. filtrationfiltered
  7. washrinsing the filter cake with water (×3)
  8. customPurification of the crude product by chromatography on silica eluting with 0-30% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-94462032679e457eaf82d424f37551fd
Source dataset
uspto-grants-2015_01
Patent number
US08937069B2

Reaction notes

Loading…