Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → (R)-ethyl 4-(biphenyl-4-yl)-3-(6-(methylsulfonamido)nicotinamido)butanoate

Participants

Reaction Steps

To a solution of (R)-ethyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride (103 mg, 0.32 mmol) and 6-(methylsulfonamido)nicotinic acid, intermediate 15, (84 mg, 0.39 mmol) in CH2Cl2 (2 mL) and DMF (2 mL) is added TEA (0.18 mL, 1.29 mmol) and HATU (159 mg, 0.42 mmol) at room temperature. The crude is stirred at room temperature for 2 hrs. The crude is quenched with saturated NaHCO3, diluted in EtOAc. The organic layer is washed with six times with water, brine, dried over MgSO4, filtered, and concentrated. The crude is purified via RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN) to give (R)-ethyl 4-(biphenyl-4-yl)-3-(6-(methylsulfonamido)nicotinamido)butanoate as a white solid (4.1 mg). HPLC retention time=1.61 minutes (condition A); MS (m+1)=482.3. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (t, J=7.2 Hz, 3H), 2.56 (t, J=4.8 Hz, 2H), 2.84-2.92 (m, 1H), 3.05 (dd, J=13.6, 6.1 Hz, 1H), 3.16 (s, 3H), 4.08-4.18 (m, 2H), 4.57-4.71 (m, 1H), 7.03 (d, J=8.3 Hz, 1H), 7.10 (d, J=8.3 Hz, 1H), 7.22 (d, J=8.3 Hz, 2H), 7.26-7.31 (m, 1H), 7.33-7.40 (m, 2H), 7.44-7.54 (m, 5H), 7.98 (dd, J=8.8, 2.3 Hz, 1H), 8.52 (s, 1H).

Provenance & Evidence