N-[2-(cyclopropylamino)-4-fluorophenyl]-5-fluoropyridine-3-carboxamide → 1-cyclopropyl-6-fluoro-2-(5-fluoropyridin-3-yl)-1H-benzimidazole
Reaction equation
[CH:1]1([NH:4][C:5]2[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=2[NH:12][C:13]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)=O)[CH2:3][CH2:2]1>C(O)(=O)C>[CH:1]1([N:4]2[C:5]3[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=3[N:12]=[C:13]2[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)[CH2:3][CH2:2]1Participants
3
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of the title compound from Step A (0.038 g, 0.131 mmol) in acetic acid (0.66 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 (30-50% ethyl acetate in hexanes) provided the title compound: LCMS m/z 272.16 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.06 (s, 1 H), 8.60 (d, J=2.7 Hz, 1 H), 8.03 (m, 1 H), 7.73 (dd, J=8.8, 4.8 Hz, 1 H), 7.30 (dd, J=8.6, 2.4 Hz, 1 H), 7.10-7.06 (m, 1 H), 3.59-3.55 (m, 1 H), 1.25-1.22 (m, 2 H), 0.83-0.80 (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 (30-50% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-2958fdc9533949e6befa986713a5354d
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382226B2
Reaction notes
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