Diisopropylethylamine → Isoquinolin-3-yl-carbamic acid (S)-3-benzyloxycarbonylamino-2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-propyl ester

To a solution of the crude isoquinolin-3-yl-carbamic acid (S)-3-benzyloxycarbonylamino-2-methylamino-propyl ester (9.0 mmol) in THF (35 mL) were added 4-nitrophenyl 2-chloro-3-fluorobenzylcarbamate (2.85 g, 8.79 mmol) and DIEA (2.3 mL, 13.2 mmol) at RT. The reaction mixture was stirred at RT for 30 min. The solvent was removed and the residue was dissolved in EtOAc (400 mL). The organic mixture was washed with NaOH (1 N, 50 mL×3), HCl (0.5 N, 50 mL), saturated NaHCO3, and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel column using a mixture of EtOAC and hexanes to give Isoquinolin-3-yl-carbamic acid (S)-3-benzyloxycarbonylamino-2-[3-(2-chloro-3-fluoro-benzyl)-1-methyl-ureido]-propyl ester (3.8 g, 71% for two steps) as white foam. LRMS (M+H+) m/z 594.2.

1. customThe solvent was removed
2. dissolutionthe residue was dissolved in EtOAc (400 mL)
3. washThe organic mixture was washed with NaOH (1 N, 50 mL×3), HCl (0.5 N, 50 mL), saturated NaHCO3, and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified on silica gel column
8. additiona mixture of EtOAC and hexanes

ORD record

ord-bf51b57b2c7641f8b12c5b3ed6f50d9d

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895582B2