Methyl morpholine oxide → (R)-4-(1-cyclopropylethylamino)-6-(3-(1,2-dihydroxyethyl)phenyl)pyrrolo[1,2-b]-pyridazine-3-carboxamide

A solution of (R)-4-(1-cyclopropylethylamino)-6-(3-vinylphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide (Example 186, 25 mg, 0.072 mmol) in THF/water (4/1 (1 mL) at 0° C. was added 4-methylmorpholine N-oxide (0.037 mL, 0.180 mmol) and osmium tetroxide (4% in water, 0.018 mL, 2.89 μmol). The reaction mixture was warmed up to rt and stirred for 16 hrs. The reaction mixture was purified on prep HPLC (condition A) to yield the title compound as a diastereomeric mixture (14 mg, 39%). HPLC (condition G): retention time=2.843 minute. LC/MS (M+H)+=m/z 381.1. 1H NMR (400 MHz, MeOD) δ ppm 8.12 (1 H, s), 7.93 (1 H, d, J=2.0 Hz), 7.71 (1 H, t, J=1.7 Hz), 7.59 (1 H, ddd, J=7.8, 1.4, 1.3 Hz), 7.37 (1 H, t, J=7.7 Hz), 7.25-7.29 (1 H, m), 7.21 (1 H, d, J=1.8 Hz), 4.75 (1 H, dd, J=7.0, 4.8 Hz), 4.12 (1 H, quin, J=6.4 Hz), 3.63-3.73 (2 H, m), 1.46 (3 H, dd, J=6.4, 0.9 Hz), 1.13-1.19 (1 H, m), 0.53-0.62 (2 H, m), 0.38-0.44 (2 H, m).

1. customThe reaction mixture was purified on prep HPLC (condition A)

ORD-Eintrag

ord-67ce04e73cf14ecf9973d6f509ac6f96

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09221826B2