Triethylamine → 2-(2-Phenyl-4-pyridyl)-4H-1,3-benzothiazine-4-one

HRID 499324Notes

Reaction equation

HRID 499324 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[C:10]1(OB(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].[C:26](OC)(=[O:34])[C:27]1[C:28](=[CH:30][CH:31]=[CH:32][CH:33]=1)[SH:29].C(N(CC)CC)C>C1(C)C(CCO)=CC=CC=1.O.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C.O>[C:10]1([C:2]2[CH:7]=[C:6]([C:8]3[S:29][C:28]4[CH:30]=[CH:31][CH:32]=[CH:33][C:27]=4[C:26](=[O:34])[N:9]=3)[CH:5]=[CH:4][N:3]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 21009Benzoic acid, 2-mercapto-, methyl esterHCID 78412Phenyl dihydrogen orthoborateHCID 5686382-Chloro-4-cyanopyridine

Product 1

HCID 597504632-(2-Phenyl-4-pyridyl)-4H-1,3-benzothiazine-4-oneYield 37.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 22728543Water ethylacetateSolventHCID 66602552Toluene-ethanol waterSolvent

Procedure

2-Chloro-4-cyanopyridine (0.40 g, 2.9 mmol), phenylboric acid (0.53 g, 4.3 mmol) and potassium carbonate (1.0 g, 7.2 mmol) were dissolved in toluene-ethanol-water (4:1:1, 30 ml), and the mixture was deairated under reduced pressure for 15 minutes. Tetrakis(triphenylphosphine)palladium (0.17 g, 0.14 mmol) was added to the mixture under nitrogen atmosphere, and the mixture was refluxed for 21 hrs. The reaction mixture was combined with ethyl acetate-water. The organic layer was washed with saturated brine and dried over an hydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude 2-phenylisonicotinenitrile. Methyl thiosalicylate (1.10 g, 6.5 mmol) and 2-phenylisonicotinenitrile (0.50 g, 2.8 mmol) was dissolved in toluene (2.0 ml), and triethylamine (1.1 ml, 7.9 mmol) was added thereto. The reaction mixture was refluxed for 18 hrs, cooled at room temperature to give precipitated crystals, which were collected by filtration. The filtrate was concentrated, subjected to a silica gel (50 g) column chromatography and eluted with hexane-ethyl acetate (2:1, v/v) to give crystals, which were combined with the previously obtained crystals and recrystallized from ethanol to give the titled compound (0.34 g, 27%) as white crystals.

Workup

  1. temperaturethe mixture was refluxed for 21 hrs
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over an hydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customto give crude 2-phenylisonicotinenitrile
  6. temperatureThe reaction mixture was refluxed for 18 hrs
  7. customto give
  8. customprecipitated crystals, which
  9. filtrationwere collected by filtration
  10. concentrationThe filtrate was concentrated
  11. washeluted with hexane-ethyl acetate (2:1
  12. customv/v) to give crystals, which
  13. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-c3fc1c05d66e45918e2bceb04cb16ca1
Source dataset
uspto-grants-2010_08
Patent number
US07767665B2

Reaction notes

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