Réaction #2122544

Équation de réaction

(S)-2-[5-(2-{4-[2-((S)-1-Benzyloxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl}-pyrimidin-5-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

K2CO3

H2O

→

title compound

Rendement 56.4%

(S)-2-(5-{2-[4-((S)-2-Pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-pyrimidin-5-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Rendement 56.4%

Solvants

MeOH

MeOH

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONThe flask was charged
2. 2
   Autreevacuated three times with H2
3. 3
   workup.ADDITIONAdditional catalyst (20 mg) was then added
4. 4
   workup.STIRRINGthe reaction mixture was stirred further for 3 h before it
5. 5
   Filtrationwas suction-filtered through diatomaceous earth (Celite®)
6. 6
   Concentrationconcentrated
7. 7
   workup.ADDITIONThe residue was diluted with MeOH
8. 8
   Filtrationfiltered through a PVDF syringe
9. 9
   Filtrationfilter (13 mm×0.45 μm)
10. 10
    Autrechromatographed (
11. 11
    Lavagegradient elution from 20% B to 100% B over 10 min on a Phenomenex-Gemini C18 column (30×100 mm, 10 μm) where A=95% water, 5% acetonitrile, 10 mM NH4OAc, B=10% water, 90% acetonitrile, 10 mM NH4OAc)
12. 12
    AutreAfter concentration of the selected test tubes by speed vacuum evaporation

Mode opératoire

A solution of (S)-2-[5-(2-{4-[2-((S)-1-Benzyloxycarbonyl-pyrrolidin-2-yl)-3H-imidazol-4-yl]-phenyl}-pyrimidin-5-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (317.1 mg, 0.48 mmol) in MeOH (1 mL) was added to a stirred suspension of 10% palladium on carbon (60 mg) and K2CO3 (70 mg) in a solution of MeOH (5 mL) and H2O (0.1 mL) at room temperature under N2. The flask was charged and evacuated three times with H2 and stirred for 3 h at atmosphere pressure. Additional catalyst (20 mg) was then added and the reaction mixture was stirred further for 3 h before it was suction-filtered through diatomaceous earth (Celite®) and concentrated. The residue was diluted with MeOH, filtered through a PVDF syringe filter (13 mm×0.45 μm), distributed into 4 pHPLC vials and chromatographed (gradient elution from 20% B to 100% B over 10 min on a Phenomenex-Gemini C18 column (30×100 mm, 10 μm) where A=95% water, 5% acetonitrile, 10 mM NH4OAc, B=10% water, 90% acetonitrile, 10 mM NH4OAc). After concentration of the selected test tubes by speed vacuum evaporation, there was isolated the title compound as a yellow solid (142.5 mg, 56% yield).

Source