Hydrochloric Acid → HCID 178495669, compound

Temperature

0 °C

(2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (526 mg, 1.14 mmol) was dissolved in DCM (15 mL) and HCl (4 M in dioxane, 3 mL, 12 mmol) was added. The reaction mixture was stirred for 2 h and then concentrated under reduced pressure. The crude residue was treated with (methoxycarbonylamino)-3-methylbutanoic acid (220 mg, 1.25 mmol), HATU (433 mg, 1.14 mmol) and DMF (11 mL), then cooled to 0° C. DIPEA (0.99 mL, 5.7 mmol) was added dropwise and the reaction mixture was immediately warmed to RT. After 45 min at RT, the mixture was diluted with EtOAc (100 mL) and washed successively with saturated aqueous NaHCO3, water and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc) to afford methyl (S)-1-((2S,4S)-2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (584 mg, 99%).

1. concentrationconcentrated under reduced pressure
2. temperaturethe reaction mixture was immediately warmed to RT
3. waitAfter 45 min at RT
4. washwashed successively with saturated aqueous NaHCO3, water and brine
5. dry with materialThe organics were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified by silica column chromatography (0% to 33% MeOH/EtOAc)

ORD record

ord-5f91b401dc5944b28cd8b72d54a7f816

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156823B2