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

Temperature

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 7) (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 ethyl acetate. The aqueous layer was extracted with ethyl acetate (×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 (ethyl acetate/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), 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 ethyl acetate
6. extractionThe aqueous layer was extracted with ethyl acetate (×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 (ethyl acetate/hexanes gradient)

ORD record

ord-cba15764970a460ab66c9acede48d4ed

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315487B2