Ammonium thiocyanate → 4-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridin-2-yl)-amide

HRID 550854Notes

Reaction equation

HRID 550854 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([CH:16]=[CH:17][CH:18]=1)[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13](Cl)=[O:14])[CH2:9][CH2:8]1.[S-:21][C:22]#[N:23].[NH4+].[NH2:25][C:26]1[C:27](Cl)=[N:28][CH:29]=[CH:30][C:31]=1[O:32][CH3:33]>CC(C)=O>[CH3:33][O:32][C:31]1[CH:30]=[CH:29][N:28]=[C:27]2[S:21][C:22]([NH:23][C:13]([N:10]3[CH2:11][CH2:12][N:7]([CH2:6][C:5]4[CH:16]=[CH:17][CH:18]=[C:3]([C:2]([F:20])([F:19])[F:1])[CH:4]=4)[CH2:8][CH2:9]3)=[O:14])=[N:25][C:26]=12

Participants

5

Reactant 3

HCID 15666Ammonium thiocyanateHCID 157900532-Chloro-4-methoxypyridin-3-amineHCID 590119604-(3-Trifluoromethyl-benzyl)-piperazine-1-carbonyl chloride

Product 1

HCID 248307674-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridin-2-yl)-amideYield 15%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A magnetically stirred mixture of 4-(3-Trifluoromethyl-benzyl)-piperazine-1-carbonyl chloride (500 mg, 1.630 mmol) in acetone (20 mL) under a nitrogen atmosphere at 25° C. was treated with ammonium thiocyanate (115 mg, 1.49 mmol). The reaction mixture was stirred at reflux for 30 min. At this time, the reaction was treated with 3-amino-2-chloro-4 methoxypyridine (215 mg, 1.34 mmol). The reaction mixture was refluxed overnight. At this time, the reaction was concentrated in vacuo, poured into water and extracted with ethyl acetate. The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 75:25 hexanes/ethyl acetate) afforded 4-(3-Trifluoromethyl-benzyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-b]pyridin-2-yl)-amide (35 mg, 15%) as white solid. LRMS for C20H20F3N5O2S (M+H)+ at m/z=451. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. temperatureat reflux for 30 min
  2. temperatureThe reaction mixture was refluxed overnight
  3. concentrationAt this time, the reaction was concentrated in vacuo
  4. additionpoured into water
  5. extractionextracted with ethyl acetate
  6. washThe organics were washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b9c63e3396864db78a3fb151593ab16a
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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