Triethylamine → 1-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-3-(methylamino)propan-1-one

To a solution of 3-[tert-butoxycarbonyl(methyl)amino]propanoic acid (14 mg, 0.07 mmol) in DMSO (445 μL) was added HATU (26 mg, 0.07 mmol) followed by the addition of triethylamine (28 mg, 38 μL, 0.27 mmol) and 3-(1H-benzimidazol-2-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)pyrazin-2-amine (20 mg, 0.07 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 h and then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc, dried (Na2SO4), filtered and concentrated. To the crude material was added 1:1 DCM:TFA (3 ml) and it was stirred for 1 h. The solvents were evaporated under reduced pressure and the crude material obtained was dissolved in DMSO and purified by reverse phase chromatography using 1-99% MeOH in H2O (0.05% HCl modifier) to obtain 1-(4-(5-amino-6-(1H-benzo[d]imidazol-2-yl)pyrazin-2-yl)-5,6-dihydropyridin-1(2H)-yl)-3-(methylamino)propan-1-one (2 mg, 7%). 1H NMR (400 MHz, MeOD) δ 8.31 (d, J=15.9 Hz, 1H), 7.81 (dd, J=6.1, 3.1 Hz, 2H), 7.52 (dd, J=6.0, 3.1 Hz, 2H), 6.88 (d, J=20.4 Hz, 1H), 4.33 (dd, J=13.5, 2.6 Hz, 2H), 3.85 (dt, J=39.3, 5.6 Hz, 2H), 2.95 (dt, J=24.1, 6.0 Hz, 2H), 2.82 (s, 1H), 2.75 (s, 4H). LC/MS m/z 378.0 [M+H]+.

1. custompartitioned between EtOAc and water
2. extractionThe aqueous layer was extracted with EtOAc
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated
6. additionTo the crude material was added 1:1 DCM
7. stirringTFA (3 ml) and it was stirred for 1 h
8. customThe solvents were evaporated under reduced pressure
9. customthe crude material obtained
10. custompurified by reverse phase chromatography

ORD record

ord-95a0cbc46d7244919b8de05b3263cc5b

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410112B2