Methanol → Trifluoroacetic acid

Participants

Reaction Steps

HATU (57.6 mg, 0.152 mmol) was added to a stirred solution of a TFA salt of 2-((S)-pyrrolidin-2-yl)-5-(4-(6-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)naphthalen-2-yl)phenyl)-1H-imidazole (47 mg), diisopropylethylamine (88 μL, 0.51 mmol) and (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (26.5 mg, 0.152 mmol) in DMF (4 mL) and the resulting mixture was stirred at ambient conditions for 2 hours. The reaction mixture was diluted with methanol (2 mL) and water (2 mL). The volatile component was removed in vacuo and the residue was purified by a reverse phase HPLC (water/methanol/TFA), repurified by a reverse phase HPLC (water/acetonitrile/ammonium acetate) and finally repurified by a reverse phase HPLC (water/methanol/TFA) to provide a TFA salt of methyl ((1S)-1-(((2S)-2-(4-(4-(6-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-4-yl)-2-naphthyl)phenyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate (33.3 mg) as yellow solid. LC-MS retention time 1.237 min; m/z 789.29 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 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 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min and an analysis time of 4 min where Solvent A was 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (TFA salt, 500 MHz, MeOD) δ ppm 8.29 (d, J=8.9 Hz, 2H), 8.15 (d, J=8.5 Hz, 1H), 8.10 (d, J=8.9 Hz, 1H), 7.95-8.03 (m, 4H), 7.93 (s, 1H), 7.84-7.91 (m, 3H), 5.69-5.72 (m, 0.2H), 5.24-5.35 (m, 1.8H), 4.27 (dd, J=7.2, 2.6 Hz, 2H), 4.09-4.19 (m, 2H), 3.85-3.97 (m, 2H), 3.67-3.76 (m, 6H), 2.55-2.68 (m, 2H), 2.27-2.38 (m, 2H), 2.14-2.27 (m, 4H), 2.02-2.14 (m, 2H), 0.86-1.06 (m, 12H).

Provenance & Evidence