5-acetyl-N-[2-(cyclopropylamino)-4-fluorophenyl]pyridine-3-carboxamide → 1-[5-(1-cyclopropyl-6-fluoro-1H-benzimidazol-2-yl)pyridin-3-yl]ethanone
Reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[NH:20][CH:21]2[CH2:23][CH2:22]2)=O)[CH:7]=[N:8][CH:9]=1)(=[O:3])[CH3:2]>C(O)(=O)C>[CH:21]1([N:20]2[C:14]3[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=3[N:12]=[C:10]2[C:6]2[CH:5]=[C:4]([C:1](=[O:3])[CH3:2])[CH:9]=[N:8][CH:7]=2)[CH2:23][CH2:22]1Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of the title compound from Step B (0.10 g, 0.32 mmol) in acetic acid (1.60 mL) was heated at 100° C. for 1 hour, then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate, washed sequentially with aqueous 1 N sodium hydroxide solution and brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (50-80% ethyl acetate in hexanes) provided the title compound: LCMS m/z 296.07 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.41 (d, J=1.9 Hz, 1 H), 9.26 (d, J=1.9 Hz, 1 H), 8.22 (m, 1 H), 7.75 (dd, J=8.8, 4.8 Hz, 1 H), 7.32 (dd, J=8.6, 2.3 Hz, 1 H), 7.10-7.06 (m, 1 H), 3.65-3.61 (m, 1 H), 2.73 (s, 3H), 1.26-1.20 (m, 2 H), 0.81-0.77 (m, 2 H).
Workup
- concentrationconcentrated under reduced pressure
- additionThe resulting residue was diluted with ethyl acetate
- washwashed sequentially with aqueous 1 N sodium hydroxide solution and brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customPurification by flash chromatography on silica gel (50-80% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-a415aba066dd4c8088611498760efe36
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382226B2
Reaction notes
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