Triethylamine → 2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-N-isopropyl-6-(methylsulfonyl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine

Temperature

0 °C

A solution of 2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (735.3 mg, 1.421 mmol) in DCM (14.2 mL) at 0° C. was treated with triethylamine (0.594 mL, 4.26 mmol), followed by methanesulfonyl chloride (0.221 mL, 2.84 mmol). The reaction mixture was stirred at 0° C. for 1 h. The reaction mixture was concentrated under reduced pressure. The residue was taken up in MeOH, filtered through a Millipore® 0.45 μm syringe filter, and purified by HPLC Method A. The corresponding fractions were collected and concentrated under reduced pressure. The resulting residue was taken up in DCM and washed with saturated aqueous K2CO3 to generate the free base. The organic layer was separated, dried over Na2SO4, and filtered. Evaporation of the filtrate and lyophilization gave the title compound as an off-white solid (229.6 mg, 33.6%). 1H NMR (500 MHz, DMSO-d6) 1.18 (d, J=6.3 Hz, 6H), 1.88 (m, 2H), 2.07 (m, 2H), 2.75 (t, J=5.9 Hz, 2H), 2.89 (m, 2H), 2.97 (s, 3H), 3.29 (m, 2H), 3.45 (t, J=5.9 Hz, 2H), 4.09 (m, 1H), 4.16 (s, 2H), 4.52 (tt, J=8.1, 3.9 Hz, 1H), 5.57 (d, J=8.3 Hz, 1H), 7.01 (m, 1H), 7.30 (m, 2H); ESI-MS m/z [M+H]+ 481.90.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. filtrationfiltered through a Millipore® 0.45 μm syringe
3. filtrationfilter
4. custompurified by HPLC Method A
5. customThe corresponding fractions were collected
6. concentrationconcentrated under reduced pressure
7. washwashed with saturated aqueous K2CO3
8. customThe organic layer was separated
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customEvaporation of the filtrate and lyophilization

ORD record

ord-beee021544244664ad3cc560aac4e3dd

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181249B2