Trifluoroacetic acid → HCID 178502482, compound

HATU (411 mg, 1.082 mmol) was added to a solution of a TFA salt of (1R,3S,5R)-3-(4-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane (525 mg, 0.902 mmol) and (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (190 mg, 1.08 mmol) in DMF (10 mL) and DIPEA (0.79 mL, 4.5 mmol) and the reaction was stirred at rt for 4 h. The reaction was diluted with EtOAc (˜80 mL) and washed with sat. aq. NaHCO3, water (30 mL) and brine (30 mL). The organics were then dried (MgSO4), filtered and concentrated to a brown oil (625 mg). This material was purified on a BIOTAGE® Horizon (40 g SiO2, 40-80% EtOAc/hexanes) to yield methyl(S)-1-((1R,3S,5R)-3-(4-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (412 mg) as a yellow glass. LC-MS retention time 1.843 min; m/z 511.24, 513.12 (1:1) (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1.0 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode.

1. washwashed with sat. aq. NaHCO3, water (30 mL) and brine (30 mL)
2. dry with materialThe organics were then dried (MgSO4)
3. filtrationfiltered
4. concentrationconcentrated to a brown oil (625 mg)
5. customThis material was purified on a BIOTAGE® Horizon (40 g SiO2, 40-80% EtOAc/hexanes)

ORD record

ord-ce34206c45614d3fa2c7962aaa71c206

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006455B2