2-Chloro-4-fluorobenzoyl chloride → 2-Chloro-4-fluoro-N-[3-fluoro-5-(1-methyl-piperidin-4-ylsulfanyl)-phenyl]-benzamide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:16])[CH:5]=[C:6]([S:8][CH:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[CH:7]=1.[Cl:17][C:18]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21]>O1CCOCC1>[Cl:17][C:18]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:19]=1[C:20]([NH:16][C:4]1[CH:5]=[C:6]([S:8][CH:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]2)[CH:7]=[C:2]([F:1])[CH:3]=1)=[O:21]Participants
4
Procedure
Combine 3-fluoro-5-(1-methyl-piperidin-4-ylsulfanyl)-phenylamine (preparation 114, 0.11 g, 0.46 mmol), 1,4-dioxane (5 mL) and 2-chloro-4-fluoro-benzoyl chloride (0.09 g, 0.46 mmole), stir and heat at reflux. After 3 hr., cool to ambient temperature. Load on an SCX column (10 g), wash with methanol, elute with 2M ammonia/methanol. Concentrate eluent. Purify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride to obtain the title compound (0.03 g, 17%). Mass spectrum: Obs. m/z 397.0974; calc. m/z 397.0953; 1H NMR (CDCl3) free base: 7.9 (bs, 1H), 7.8 (m, 1H), 7.4 (m, 1H), 7.3 (s, 1H), 7.2 (m, 1H), 7.1 (m, 1H), 6.9 (m, 1H), 3.2 (m, 1H), 2.8 (m, 2H), 2.3 (s, 3H), 2.0 (m, 4H), 1.7 (m, 2H).
Workup
- temperatureheat
- temperatureat reflux
- washLoad on an SCX column (10 g), wash with methanol
- washelute with 2M ammonia/methanol
- washPurify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride
Sources & evidence
- ORD record
- ord-2dab5e8d24534821b0eff623762850c3
- Source dataset
- uspto-grants-2009_10
- Patent number
- US07608629B2
Reaction notes
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