Sodium triacetoxyborohydride → (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoate

Temperatur

22.5 °C

To a 100 mL round-bottomed flask with a magnetic stir bar were added (R)-N-(pyrrolidin-3-yl)isoquinolin-5-amine scuccinic acid salt (2.00 g, 6.04 mmol, from Example 5), tetrahydrofuran (30 mL), and 2-(3-formylphenoxy)ethyl benzoate (1.63 g, 6.04 mmol). The mixture was stirred at 20 to 25° C. for 15 minutes. To the mixture was added sodium triacetoxyborohydride (1.92 g, 9.05 mmol). The mixture was stirred at 20 to 25° C. for 20 hours. The reaction was quenched with 20 mL of 15% Na2CO3 (final pH ˜10). Tetrahydrofuran was removed by distillation under vacuum. The residue was extracted with 30 mL of methyl tert-butyl ether. The organic layer was washed with 30 mL of water (twice) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-12% methanol/dichloromethane) to give (R)-2-(3-((3-(isoquinolin-5-ylamino)pyrrolidin-1-yl)methyl)phenoxy)ethyl benzoate as a oil (2.57 g, 91% yield).

1. stirringThe mixture was stirred at 20 to 25° C. for 20 hours
2. customThe reaction was quenched with 20 mL of 15% Na2CO3 (final pH ˜10)
3. customTetrahydrofuran was removed by distillation under vacuum
4. extractionThe residue was extracted with 30 mL of methyl tert-butyl ether
5. washThe organic layer was washed with 30 mL of water (twice) and
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography (0-12% methanol/dichloromethane)

ORD-Eintrag

ord-ed35e0640d224317bdbec9b861b8a4ce

Quelldatensatz

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08158796B2