Serinol → 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(1,3-dihydroxypropan-2-yl)benzamide

Participants

Reaction Steps

To a flask charged with 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 4) (90 mg, 0.211 mmol) and HATU (96 mg, 0.253 mmol) was added DMF (3 mL) and the resulting mixture was treated with DIPEA (0.111 mL, 0.633 mmol). After 5 min, the mixture was treated with 2-aminopropane-1,3-diol (38.5 mg, 0.422 mmol). The reaction mixture was stirred for 1 h, whereupon the bulk of solvent was removed and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The phases were separated and the aqueous phase was extracted with EtOAc (×2). The combined organic layers were washed with saturated aqueous NaHCO3 (×3), then brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by MDAP (HpH). The appropriate fractions were collected and concentrated in vacuo. The residue was dissolved in MeOH and dried (hydrophobic frit). The solvent was then removed in vacuo and the residue triturated with Et2O to give 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(1,3-dihydroxypropan-2-yl)benzamide (32 mg, 0.064 mmol, 30% yield) as a white solid. LCMS (HpH, 2 min), Rt=0.75 min, MH+=500.

Provenance & Evidence