Diisopropylethylamine → 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide

In a 100 mL round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.0 g, 2.69 mmol) was combined with dichloromethane (3 ml) to give a yellow solution. (R)-1-Benzylpyrrolidin-3-amine (710 mg, 4.03 mmol) and then DIEA (1.88 ml, 10.7 mmol) were added. To the clear solution was added HATU (2.04 g, 5.37 mmol) and to this mixture was added DMF (4 ml). The reaction was stirred under nitrogen overnight then concentrated and partioned between water (100 ml) and EtOAc (100 ml). The aqueous layer was washed with EtOAc (50 ml) then the combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude was dissolved in EtOAc, supported on silica gel, and purified by flash chromatography (120 g silicycle) with 0% to 100% EtOAc in hexanes. The appropriate fractions combined and concentrated to yield 1.38 g (97%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide as a clear viscous semisolid with a slight red/brown tint. LC-MS (M+H)+=530.

1. customto give a yellow solution
2. concentrationthen concentrated
3. washThe aqueous layer was washed with EtOAc (50 ml)
4. washthe combined organics were washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe crude was dissolved in EtOAc
9. custompurified by flash chromatography (120 g silicycle) with 0% to 100% EtOAc in hexanes
10. concentrationconcentrated

ORD record

ord-8194ed0f88a842a486477abeda3e2504

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2