p-Toluenesulfonic acid monohydrate → 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide (142.4 mg, 0.26 mmol) in methanol (2.6 mL, 0.10M) at 25° C. was treated with para-toluenesulfonic acid monohydrate (7.7 mg, 0.04 mmol). The reaction was stirred at 25° C. overnight. After this time, the reaction was concentrated in vacuo. Silica gel column chromatography (AnaLogix 8 g, 1-10% methanol/methylene chloride) afforded 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-propionamide (110.3 mg, 84%) as an off-white solid as a mixture of diastereomers; ES+-HRMS m/e calcd for C24H27N5O5F2 [M+H+] 504.2053 found 504.2053. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.03-1.18 (m, 1H) 1.22-1.76 (m, 8H) 1.88-2.01 (m, 1H) 2.17-2.35 (m, 1H) 3.19-3.32 (m, 2H) 3.70-3.80 (m, 1H) 3.82-3.93 (m, 1H) 4.09 (dd, J=13.3, 4.4 Hz, 1H) 4.70 (t, J=5.5 Hz, 1H) 4.94 (dd, J=5.5, 2.5 Hz, 1H) 5.40-5.51 (m, 1H) 6.03 (d, J=3.0 Hz, 1H) 6.36 (d, J=2.1 Hz, 1H) 7.35-7.43 (m, 2H) 7.44-7.51 (m, 1H) 7.53 (d, J=2.1 Hz, 1H) 8.28 (d, J=3.0 Hz, 1H) 10.83 (s, 1H).

Provenance & Evidence