Benzenethiol, 2-amino-3,4,6-trifluoro-, hydrochloride → 6-Ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid-methyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[N:7][C:8]([CH2:14][CH3:15])=[C:9]([CH2:11][C:12]#[N:13])[CH:10]=1.Cl.N[C:19]1[C:24]([F:25])=[C:23]([F:26])[CH:22]=[C:21]([F:27])[C:20]=1[SH:28]>>[CH3:1][O:2][C:3](=[O:16])[CH2:4][C:5]1[CH:6]=[N:7][C:8]([CH2:14][CH3:15])=[C:9]([CH2:11][C:12]2[S:28][C:20]3[C:21]([F:27])=[CH:22][C:23]([F:26])=[C:24]([F:25])[C:19]=3[N:13]=2)[CH:10]=1Participants
Conditions
- Temperature
- 120 °C
Procedure
A mixture of 5-cyanomethyl-6-ethyl-pyridin-3-yl-acetic acid methyl ester (0.51 g, 2.34 mmol), 2-amino-3,4,6-trifluorothiophenol hydrochloride (0.54 g, 2.53 mmol) and BHT (10 mg) in a sealed reaction vessel is heated to 120° C. for 9 h. After cooling to room temperatue, the resulting slurry is adsorbed onto silica gel and purified by flash column chromatography (10-30% ethyl acetate in hexanes) to give 6-ethyl-5-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyridin-3-yl-acetic acid-methyl ester as a yellow oil (0.70 g, 79%): Rf 0.36 (50% ethyl acetate in n-heptane), 1H NMR (CDCl3, 300 MHz) δ 8.46 (s, 1 H), 7.64 (s, 1 H), 7.08-6.97 (m, 1 H), 4.50 (s, 2 H), 3.72 (s, 3 H), 3.65 (s, 2 H), 2.90 (q, J=7.4 Hz, 2 H), 1.29 (t, J=7.4 Hz, 3 H); ESI-LCMS m/z calcd for C18H15F3N2O2S: 380.1; found 381.0 (M+1)+.
Workup
- customin a sealed reaction vessel
- temperatureAfter cooling to room temperatue
- custompurified by flash column chromatography (10-30% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-393b80ce9eec4a028948bc8ee0525d42
- Source dataset
- uspto-grants-2008_04
- Patent number
- US07361671B2
Reaction notes
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