Diisopropylethylamine → HCID 70872615, compound

A stirred solution of methyl 5-bromo-2-methyl-3-[(oxan-4-yl)(2,2,2-trifluoroethyl)amino]benzoate (250 mg, 0.63 mmol) in dry DMF (3.0 ml) at 0° C. under a balloon of nitrogen, was treated with HATU (288 mg, 0.76 mmol) and DIPEA (220 μl, 1.3 mmol) dropwise. The resulting solution was stirred for 5 minutes and then treated with 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 119 mg, 0.69 mmol). The resulting suspension was stirred at 0° C. for 20 minutes and then stirred at room temperature for 16.5 hours. The reaction mixture was treated with 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (30 mg). Stirring was continued for further 23 hours and the reaction mixture was then partitioned between water (30 ml) and CH2Cl2 (20 ml). The layers were separated and the aqueous phase was extracted with CH2Cl2 (3×20 ml). The combined organics were washed with a saturated solution of NaHCO3 (aq) (50 ml), water (60 ml), brine (2×40 ml), dried over MgSO4, filtered and concentrated in-vacuo. The crude residue was purified by flash column chromatography (10 g SNAP cartridge, Isolera, 0-10% MeOH/CH2Cl2) and triturated from ether (10 ml) with sonication. The resulting precipitate was collected by filtration and dried in-vacuo to give the title compound (249 mg, 74%) as a white solid. LC-MS 100%, 4.08 min (7 minute LC-MS method), m/z=530.0, 531.0, 532.0, 533.0; 1H NMR (500 MHz, Acetone) δ 10.67 (s, 1H), 7.55 (d, J=1.8 Hz, 2H), 7.27 (d, J=1.9 Hz, 1H), 5.90 (s, 1H), 4.40 (d, J=5.5 Hz, 2H), 3.90 (dd, J=11.2, 4.6 Hz, 4H), 3.28 (t, J=11.6 Hz, 2H), 3.07-2.97 (m, 1H), 2.32 (s, 3H), 2.29 (s, 3H), 2.24 (s, 3H), 1.76 (dd, J=12.3, 1.6 Hz, 2H), 1.61 (qd, J=12.0, 4.5 Hz, 2H).

1. stirringThe resulting suspension was stirred at 0° C. for 20 minutes
2. stirringstirred at room temperature for 16.5 hours
3. stirringStirring
4. waitwas continued for further 23 hours
5. customthe reaction mixture was then partitioned between water (30 ml) and CH2Cl2 (20 ml)
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with CH2Cl2 (3×20 ml)
8. washThe combined organics were washed with a saturated solution of NaHCO3 (aq) (50 ml), water (60 ml), brine (2×40 ml)
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in-vacuo
12. customThe crude residue was purified by flash column chromatography (10 g SNAP cartridge, Isolera, 0-10% MeOH/CH2Cl2)
13. customtriturated from ether (10 ml) with sonication
14. filtrationThe resulting precipitate was collected by filtration
15. customdried in-vacuo

ORD record

ord-5198d4d955e3450c9b118ad9f2f1400a

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410088B2