Diisopropylethylamine → 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Temperatur

200 °C

To a mixture of 1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 1)(2.28 g, 8.05 mmol) and 6-chloronicotinonitrile (2.231 g, 16.10 mmol) was added NMP (20 mL) and the mixture treated with DIPEA (4.22 mL, 24.16 mmol). The mixture was split between 2 flasks and each flask was flushed with nitrogen, sealed and stirred under microwave irradiation at 200° C. for 2 h. The reaction mixtures were combined and partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (×4) and the combined organic layers were washed with water (×3), then brine and were dried (MgSO4) filtered and concentrated in vacuo. The brown solid residue was purified by chromatography (EtOAc in Hexanes gradient) to give 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (1.940 g, 5.04 mmol, 62.5% yield) as a pale yellow foam. LCMS (HpH, 2 min), Rt=1.02 min, MH+=386 (1 Br).

1. customThe mixture was split between 2 flasks and each flask
2. customwas flushed with nitrogen
3. customsealed
4. customThe reaction mixtures
5. custompartitioned between water and EtOAc
6. extractionThe aqueous layer was extracted with EtOAc (×4)
7. washthe combined organic layers were washed with water (×3)
8. dry with materialbrine and were dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe brown solid residue was purified by chromatography (EtOAc in Hexanes gradient)

ORD-Eintrag

ord-aaa3ad66e371440a82336f90ad0dcba6

Quelldatensatz

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08993554B2