Triethylamine → 4-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)amide

HRID 907543Notes

Reaction equation

HRID 907543 reaction equation
[Cl:1][C:2]1[C:3]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[N:4][S:5][N:6]=1.C(N(CC)CC)C.[N:20]([C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1)=[C:21]=[O:22]>C(Cl)Cl.CCOC(C)=O>[F:30][C:29]([F:31])([F:32])[C:27]1[CH:28]=[C:23]([NH:20][C:21]([N:10]2[CH2:9][CH2:8][N:7]([C:3]3[C:2]([Cl:1])=[N:6][S:5][N:4]=3)[CH2:12][CH2:11]2)=[O:22])[CH:24]=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 15524002HCID 15524002, compound

Product 1

HCID 590137964-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)amideYield 79%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-(4-chloro-[1,2,5]thiadiazol-3-yl)-piperazine (7.8 g, 32.6 mmol, 1.0 eq.), dry CH2Cl2 (130 mL), triethyl amine (11.66 g, 16 mL, 115.2 mmol, 3.5 eq). To this mixture cooled in an ice bath was added 1-isocyanato-3,5-bis-trifluoromethyl-benzene (11.6 g, 7.9 ml, 45 mmol, 1.4 eq.) dissolved in dry CH2Cl2 (20 mL) dropwise. The resulting mixture was allowed to warm up to room temperature with stirring. After stirring for 3 hour, the reaction mixture was diluted with EtOAc. This solution was then washed with aqNaHCO3, and brine. The organic layer was dried with Na2SO4, concentrated. The residue was purified by column chromatography using acetate/hexane (1:1 to 3:1), affording 4-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (11.8 g, 79% yield) as a solid.

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. temperatureTo this mixture cooled in an ice bath
  3. stirringAfter stirring for 3 hour
  4. washThis solution was then washed with aqNaHCO3, and brine
  5. dry with materialThe organic layer was dried with Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-51dcc24249874f5394c48e0d73933eef
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

Loading…