Methyl morpholine oxide → (R)-4-(1-cyclopropylethylamino)-6-(3-(1,2-dihydroxyethyl)phenyl)pyrrolo[1,2-b]-pyridazine-3-carboxamide
Reaction equation
[CH:1]1([C@H:4]([NH:6][C:7]2[C:8]3[N:9]([CH:16]=[C:17]([C:19]4[CH:24]=CC=C(C=C)[CH:20]=4)[CH:18]=3)[N:10]=[CH:11][C:12]=2[C:13]([NH2:15])=O)[CH3:5])[CH2:3][CH2:2]1.C[N+]1([O-])CC[O:31][CH2:30]C1.[CH2:35]1[CH2:39][O:38][CH2:37][CH2:36]1.[OH2:40]>[Os](=O)(=O)(=O)=O>[CH:1]1([CH:4]([NH:6][C:7]2[C:8]3[N:9]([CH:16]=[C:17]([C:19]4[CH:24]=[CH:37][CH:36]=[C:35]([C@@H:39]([OH:38])[CH2:30][OH:31])[CH:20]=4)[CH:18]=3)[N:10]=[CH:11][C:12]=2[C:13]([NH2:15])=[O:40])[CH3:5])[CH2:3][CH2:2]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
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).
Workup
- customThe reaction mixture was purified on prep HPLC (condition A)
Sources & evidence
- ORD record
- ord-67ce04e73cf14ecf9973d6f509ac6f96
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221826B2
Reaction notes
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