Acetic Acid → 2,6-Dimethyl-5-(4,5,7-trifluorobenzothiazole-2-yl-methyl)-pyridin-3-yl-acetonitrile

HRID 900967Notes

Reaction equation

HRID 900967 reaction equation
[C:1]([CH2:3][C:4]1[CH:5]=[C:6]([CH2:12][C:13]#[N:14])[C:7]([CH3:11])=[N:8][C:9]=1[CH3:10])#[N:2].Cl.N[C:17]1[C:22]([F:23])=[C:21]([F:24])[CH:20]=[C:19]([F:25])[C:18]=1[SH:26].C(O)(=O)C.C(=O)(O)[O-].[Na+]>FC(F)(F)CO.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>[CH3:10][C:9]1[C:4]([CH2:3][C:1]#[N:2])=[CH:5][C:6]([CH2:12][C:13]2[S:26][C:18]3[C:19]([F:25])=[CH:20][C:21]([F:24])=[C:22]([F:23])[C:17]=3[N:14]=2)=[C:7]([CH3:11])[N:8]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 11390282Benzenethiol, 2-amino-3,4,6-trifluoro-, hydrochlorideHCID 689391815-Cyanomethyl-2,6-dimethyl-pyridin-3-yl-acetonitrile

Product 1

HCID 689391512,6-Dimethyl-5-(4,5,7-trifluorobenzothiazole-2-yl-methyl)-pyridin-3-yl-acetonitrileYield 39.1%

Reagents, catalysts & solvents 2

HCID 314042,6-Di-tert-butyl-4-methylphenolCatalystHCID 64092,2,2-TrifluoroethanolSolvent

Procedure

In a teflon screwcap glass pressure vessel a solution of 5-cyanomethyl-2,6-dimethyl-pyridin-3-yl-acetonitrile (1.5 g, 8.1 mmol), 2-amino-3,4,6-trifluoro-benzenethiol hydrochloride (2.6 g, 12.2 mmol), 2,6-di-tert-butyl-4-methylphenol (BHT) (20 mg) and acetic acid (0.56 mL, 9.8 mmol) in 2,2,2-trifluoroethanol (10 mL, 0.8 M, degassed with nitrogen) is warmed to 90° C. and stirred overnight. The mixture is cooled to room temperature, added to saturated aq sodium bicarbonate (30 mL), extracted with ethyl acetate (2×30 mL) and dried over sodium sulfate. Purification by medium-pressure liquid chromatography (MPLC) on silica (10-90% ethyl acetate in heptane) afford 2,6-dimethyl-5-(4,5,7-trifluorobenzothiazole-2-yl-methyl)-pyridin-3-yl-acetonitrile as a white solid (1.1 g, 38%); Rf 0.37 (20% ethyl acetate in heptane); 1H NMR (DMSO-d6, 300 MHz) δ 7.71 (ddd, J=10.3, 8.5, 5.4 Hz, 1H), 7.67 (s, 1 H), 4.61 (s, 2 H), 4.03 (s, 2 H), 2.44 (s, 3 H), 2.43 (s, 3 H). ESI-LCMS m/z calcd for C17H12F3N3S: 347.1; found 348.0 (M+1)+.

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. dry with materialdried over sodium sulfate
  3. customPurification by medium-pressure liquid chromatography (MPLC) on silica (10-90% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-1828a5e135fe41c081386da2f4a12c08
Source dataset
uspto-grants-2008_04
Patent number
US07361671B2

Reaction notes

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