反应详情

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.

1. customwas removed
2. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with EtOAc (×2)
5. washThe combined organic layers were washed with saturated aqueous NaHCO3 (×3)
6. dry with materialbrine, dried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by MDAP (HpH)
9. customThe appropriate fractions were collected
10. concentrationconcentrated in vacuo
11. dissolutionThe residue was dissolved in MeOH
12. customdried (hydrophobic frit)
13. customThe solvent was then removed in vacuo
14. customthe residue triturated with Et2O