Triethylamine → Cyclopropyl(2-(4-(2,4-difluorophenoxy)piperidin-1-yl)-3-(isopropylamino)-7,8-dihydropyrido[3,4-b]pyrazin-6(5H)-yl)methanone

To 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 (18.0 mg, 0.035 mmol) in DCM (348 μL) at room temperature was added triethylamine (14.5 μL, 0.104 mmol) and cyclopropanecarbonyl chloride (6.4 μL, 0.070 mmol). The reaction was stirred for 10 min at room temperature. The reaction mixture was concentrated under reduced pressure and was purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column was used, using a 50% to 90% ACN gradient to give the title compound, as a TFA salt, as a yellow film (3.3 mg, 16%). 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 0.81-0.96 (m, 4H), 1.29 (m, 7H), 1.90-2.18 (m, 4H), 2.73 (m, 0.7H), 2.87 (m, 1.3H), 3.07 (m, 2H), 3.42 (m, 2H), 3.88 (m, 0.7H), 4.06 (t, J=5.7 Hz, 1.3H), 4.14 (m, 1H), 4.49 (m, 1H), 4.62 (s, 1.3H), 4.80 (s, 0.7H), 6.88 (m, 1H), 6.99 (ddd, J=11.2, 8.5, 3.0 Hz, 1H), 7.18 ppm (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 472.5.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customwas purified by HPLC Method B, with the exception that a Waters SunFire™ C18, 5 μm, ID 30×75 mm column

ORD record

ord-444270cf2bfe4c5dbd5f79bbe0b98401

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181249B2