Diisopropylethylamine → HCID 44464039, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclobutyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 29, 151.8 mg, 0.43 mmol) in N,N-dimethylformamide (1.67 mL, 0.26M) at 25° C. was treated with N,N-diisopropylethylamine (0.21 mL, 1.29 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (0.28 g, 0.64 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1, 0.08 g, 0.51 mmol). The reaction was stirred at 25° C. overnight. After this time, the reaction was diluted with ethyl acetate (100 mL) and was washed with a saturated aqueous ammonium chloride solution (1×150 mL), a saturated aqueous sodium bicarbonate solution (1×150 mL) and a saturated aqueous sodium chloride solution (1×150 mL), dried over sodium sulfate, filtered, rinsed and concentrated in vacuo. Silica gel column chromatography (AnaLogix 12 g, 75-100% gradient ethyl acetate/hexanes) afforded 3-cyclobutyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide (107 mg, 51%) as an off-white solid; ES+-HRMS m/e calcd for C24H27N5O4F2 [M+H+] 488.2104 found 488.2103. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.06 (br s, 3H) 1.07 (br s, 3H) 1.45-1.66 (m, 1H) 1.69-1.89 (m, 4H) 1.88-2.03 (m, 1H) 2.02-2.41 (m, 3H) 3.90 (s, 2H) 4.67 (s, 1H) 5.35 (dd, J=10.1, 4.4 Hz, 1H) 6.02 (d, J=2.9 Hz, 1H) 6.40 (d, J=2.1 Hz, 1H) 7.34-7.44 (m, 2H) 7.44-7.51 (m, 1H) 7.53 (d, J=2.1 Hz, 1H) 8.27 (d, J=2.9 Hz, 1H) 10.83 (s, 1H).

Provenance & Evidence