Hexane → 2-((2-(6-Amino-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanol

A suspension of tris(dibenzylideneacetone)dipalladium(0) (48 mg, 0.053 mmol) in anhydrous THF (3 mL) was treated with tri-t-butylphosphine in hexane (10% wt) (0.320 mL, 0.105 mmol) and the mixture stirred for 5 minutes at room temperature. A solution of 2-((2-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanol (compound 2, 0.165 g, 0.527 mmol) in THF (7 mL) was added followed by lithium bis(trimethylsilyl)amide (1M in THF, 1.58 mL, 1.58 mmol) and the mixture heated in a sealed reaction vial at 90° C. for 3 hours. The mixture was cooled to room temperature then to 0° C. and quenched with 3N aq. HCl (1.5 mL) and stirred for 30 minutes slowly warming to room temperature. The mixture was diluted with ethyl acetate, basified to pH ˜10 by the addition of 1N aq NaOH and transferred to a separatory funnel. The organic layer was separated and the aqueous layer further extracted with ethyl acetate (×3) and the combined organic layers washed with brine, dried over Na2SO4, filtered and concentrated to give a dark brown residue. Purification on silica gel eluting with 7.5% 2M NH3 in methanol/92.5% dichloromethane yielded an orange-red residue, 3 (57 mg, 43.4%). 1H-NMR (DMSO-d6) δ 6.36-6.27 (m, 2H), 6.21 (br s, 1H), 4.31 (t, 1H, J=5.4 Hz, exch. D2O), 4.18 (br s, 2H, exch. D2O), 3.44 (q, 2H, J=6.3 Hz), 3.18 (t, 2H, J=7.3 Hz), 3.10 (t, 2H, J=5.3 Hz), 2.56-2.40 (2×m, 6H), 2.22 (s, 3H), 1.84-1.72 (m, 2H). MS (ESI+): 250 (MH+, 100).

1. temperaturethe mixture heated in a sealed reaction vial at 90° C. for 3 hours
2. temperatureThe mixture was cooled to room temperature
3. customto 0° C. and quenched with 3N aq. HCl (1.5 mL)
4. stirringstirred for 30 minutes
5. temperatureslowly warming to room temperature
6. additionThe mixture was diluted with ethyl acetate
7. additionbasified to pH ˜10 by the addition of 1N aq NaOH
8. customtransferred to a separatory funnel
9. customThe organic layer was separated
10. extractionthe aqueous layer further extracted with ethyl acetate (×3)
11. washthe combined organic layers washed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. customto give a dark brown residue
16. customPurification on silica gel eluting with 7.5% 2M NH3 in methanol/92.5% dichloromethane

ORD record

ord-6dc971c0d0364563bb244839c2f09883

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173813B2