N,N-Dimethylethylenediamine → HCID 86709415, compound

Participants

Reaction Steps

To a flask charged with 4-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 31)(4.88 g, 11.50 mmol) and HATU (5.25 g, 13.80 mmol) was added DMF (2 mL). The resulting mixture was treated with DIPEA (6.02 mL, 34.5 mmol) then after 5 min with N1,N1-dimethylethane-1,2-diamine (1.317 g, 14.95 mmol). After 0.5 h most of the DMF was removed in vacuo. The residue was treated with EtOAc and saturated NaHCO3. Insoluble solid appeared which was isolated by filtration and dried under vacuum at 60° C. for 3 h to give tert-butyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate as white solid (8.5 g), which was used without further purification in the subsequent reaction. The phases of the filtrate were separated, and the aqueous extracted with EtOAc (×2). The combined organic phases were washed with saturated NaHCO3(×3), dried over MgSO4 and concentrated in vacuo to give a liquid (2.1 g). This liquid was loaded onto a SCX cartridge (50 g, pre-conditioned with MeOH) the cartridge washed with MeOH (200 ml) and eluted with ammonia in MeOH (2M, 200 ml). The methanolic ammonia fractions were combined and concentrated in vacuo to give a further portion of tert-butyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (0.3 g, 0.6 mmol, 5% yield) as an orange solid. LCMS (Formate, 2 min), Rt=0.94 min, MH+=495.

Provenance & Evidence