反应详情

A solution of 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) in DMF (2 mL) was treated with EDC (48.5 mg, 0.253 mmol), HOBT hydrochloride (38.8 mg, 0.253 mmol) and N-ethylmorpholine (0.080 mL, 0.633 mmol) and after 3 min with (S)-3-aminopropane-1,2-diol (38.5 mg, 0.422 mmol). The resulting mixture was stirred at room temperature for 5 h then EDC (48.5 mg, 0.253 mmol), N-ethyl morpholine (0.080 mL, 0.633 mmol), HOBT (38.8 mg, 0.253 mmol) and further (S)-3-aminopropane-1,2-diol (38.5 mg, 0.422 mmol) were added and the corresponding mixture was stirred for 16 h then concentrated in vacuo. The residue was partitioned between water and EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc (×2) and 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 to give 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N—((S)-2,3-dihydroxypropyl)benzamide (30 mg, 29%) as a white solid. LCMS (HpH, 2 min), Rt=0.75 min, MH+=500.

1. stirringthe corresponding mixture was stirred for 16 h
2. concentrationthen concentrated in vacuo
3. customThe residue was partitioned between water and EtOAc
4. customthe layers were separated
5. extractionThe aqueous phase was extracted with EtOAc (×2)
6. washthe combined organic layers were washed with saturated aqueous NaHCO3 (×3)
7. dry with materialbrine, dried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by MDAP