Benzophenone imine → 5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamine

HRID 905926Notes

Reaction equation

HRID 905926 reaction equation
Br[C:2]1[N:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2=[N:6][CH:7]=1.C(=[NH:32])(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])(=O)C.[Na+].Cl.NO>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:16][Si:15]([CH3:18])([CH3:17])[CH2:14][CH2:13][O:12][CH2:11][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([NH2:32])[N:3]=[C:4]2[CH:10]=[CH:9]1

Participants

8

Reactant 4

HCID 136809Benzophenone imineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 575165972-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine

Product 1

HCID 593633695-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamineYield 113.5%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (3.25 g, 10 mmol) sodium t-butoxide (0.600 g, 6.25 mmol), and BINAP (0.170 g, 0.27 mmol) in 120 mL of toluene was purged with nitrogen for ca. 20 min. Pd2(dba)3 (0.080 g, 0.077 mmol) and benzophenone imine (2.16 mL, 12.9 mmol) were added, and the mixture was stirred at 130° C. for 12 h. The mixture was filtered through Celite and concentrated. The resulting residue was dissolved in 50 mL of methanol. Sodium acetate (4.93 g, 36 mmol) and hydroxylamine hydrochloride (2.09 g, 30 mmol) were added, and the mixture was stirred for 45 min. then concentrated. The resulting residue was partitioned between a 0.1 M NaOH solution and dichloromethane, and the organic layer was dried over Na2SO4, filtered and concentrated to a residue. Column chromatography afforded 3.0 g (75%) of 5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamine.

Workup

  1. customwas purged with nitrogen for ca. 20 min
  2. filtrationThe mixture was filtered through Celite
  3. concentrationconcentrated
  4. dissolutionThe resulting residue was dissolved in 50 mL of methanol
  5. stirringthe mixture was stirred for 45 min.
  6. concentrationthen concentrated
  7. customThe resulting residue was partitioned between a 0.1 M NaOH solution and dichloromethane
  8. dry with materialthe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-24edd7487fe748e4a22e3c8982ef7b18
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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