N-[2-(cyclopropylamino)-4,5-difluorophenyl]-5-(2-hydroxypropan-2-yl)pyridine-3-carboxamide → 2-[5-(1-Cyclopropyl-5,6-difluoro-1H-benzimidazol-2-yl)pyridin-3-yl]propan-2-ol
Reaction equation
[CH:1]1([NH:4][C:5]2[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=2[NH:13][C:14]([C:16]2[CH:17]=[N:18][CH:19]=[C:20]([C:22]([OH:25])([CH3:24])[CH3:23])[CH:21]=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])[C:8]([F:12])=[CH:7][C:6]=3[N:13]=[C:14]2[C:16]2[CH:21]=[C:20]([C:22]([OH:25])([CH3:24])[CH3:23])[CH:19]=[N:18][CH:17]=2)[CH2:3][CH2:2]1Participants
Procedure
A solution of the title compound from Step D (0.070 g, 0.20 mmol) in acetic acid (1.0 mL) was heated at 100° C. for 1 hour, and then cooled to room temperature. The resulting mixture was concentrated under reduced pressure, 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 acetated in hexanes) provided the title compound: LCMS m/z 330.04 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.09 (s, 1 H), 8.87 (s, 1 H), 8.44 (d, J=1.8 Hz, 1 H), 7.58 (dd, J=10.3, 7.3 Hz, 1 H), 7.40 (dd, J=9.7, 7.0 Hz, 1 H), 3.59-3.58 (m, 1 H), 2.89 (br s, 1 H), 1.69 (s, 6 H), 1.22-1.19 (m, 2 H), 0.79-0.78 (m, 2 H).
Workup
- concentrationThe resulting mixture was concentrated under reduced pressure
- additiondiluted 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 acetated in hexanes)
Sources & evidence
- ORD record
- ord-6e0532738bd549c4b51381bd1b3ee08d
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382226B2
Reaction notes
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