Ammonium thiocyanate → HCID 11303237, compound

HRID 2106094Notes

Reaction equation

HRID 2106094 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:17]=1[F:23].[NH4+].[N:25]#[C:26][S-:27].BrBr>CC(O)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:17]([F:23])=[CH:18][C:19]2[N:22]=[C:26]([NH2:25])[S:27][C:20]=2[CH:21]=1

Participants

5

Reactant 3

HCID 15666Ammonium thiocyanate2×HCID 24408Bromine2×HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamine

Product 1

HCID 11303237HCID 11303237, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent3×

Procedure

4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylamine (1.00 g, 3.18 mmol) was dissolved in AcOH (8.0 ml), to which was added NH4SCN (486 mg, 6.38 mmol) and the mixture cooled in an ice bath. Br2 (0.33 ml, 6.42 mmol) in AcOH (0.33 ml) was added dropwise with stirring. After addition was complete, the reaction mixture was stirred at room temperature. After one hour, more NH4SCN (1.0 g, 13.1 mmol) was added, followed by more Br2 (0.33 ml, 6.42 mmol) in AcOH (0.33 ml), dropwise with stirring. The reaction mixture was then heated to reflux for several minutes. Upon cooling to room temperature, solids were filtered and washed with AcOH, followed by H2O. The volume of the filtrate was reduced in vacuo and the pH adjusted to pH 9-10 with 1.0N NaOH. The resulting solids were filtered, washed with H2O, and dried under high vacuum to give 6-(6,7-dimethoxy-quinolin-4-yloxy)-5-fluoro-benzothiazol-2-ylamine (568 mg, 48%). 1H-NMR (400 MHz, DMSO): 8.45 (d, 1H), 7.82 (d, 1H), 7.73 (br s, 2H), 7.53 (s, 1H), 7.38 (m, 2H), 6.44 (d, 1H), 3.94 (s, 6H). LC/MS Calcd for [M+H]+ 372.1, found 372.2

Workup

  1. temperaturethe mixture cooled in an ice bath
  2. additionAfter addition
  3. stirringthe reaction mixture was stirred at room temperature
  4. stirringdropwise with stirring
  5. temperatureThe reaction mixture was then heated
  6. temperatureto reflux for several minutes
  7. filtrationsolids were filtered
  8. washwashed with AcOH
  9. filtrationThe resulting solids were filtered
  10. washwashed with H2O
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-bb75f1817955464f8d016b9a75e30a9a
Source dataset
uspto-grants-2009_08
Patent number
US07579473B2

Reaction notes

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