Methanol → Trifluoroacetic acid

Participants

Reaction Steps

HATU (20 mg, 0.053 mmol) was added to a mixture of a TFA salt of 2-((S)-pyrrolidin-2-yl)-6-(7-(2-((S)-pyrrolidin-2-yl)-1H-imidazol-4-yl)naphthalen-2-yl)-1H-benzo[d]imidazole (16 mg), diisopropylethylamine (31 μL, 0.18 mmol) and (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (9.3 mg, 0.053 mmol) in DMF (2 mL) and the resulting mixture was stirred at ambient for 9 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/acetonitrile 0.1% TFA) to provide a TFA salt of methyl ((1S)-1-(((2S)-2-(4-(7-(2-((2S)-1-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-benzimidazol-5-yl)-2-naphthyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate (7.9 mg) as white solid. LC-MS retention time 1.20 min; calcd. for C42H50N8O6 762.39. found m/z 763.35 [M+H]+. 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. 1H NMR (500 MHz, MeOD) δ ppm 8.35 (s, 1H), 8.25 (s, 1H), 8.09 (dd, J=8.4, 3.2 Hz, 2H), 8.04 (s, 1H), 7.89-8.00 (m, 3H), 7.77-7.87 (m, 2H), 5.37 (t, J=7.0 Hz, 1H), 5.30 (t, J=7.3 Hz, 1H), 4.28 (dd, J=15.4, 7.2 Hz, 2H), 4.08-4.20 (m, 2H), 3.86-4.01 (m, 2H), 3.69 (s, 6H), 2.56-2.68 (m, 3H), 2.39-2.02 (m, 7H), 0.87-1.04 (m, 12H).

Provenance & Evidence