Triethylamine → trans-2',4'-Dibromo-4-(4-cyano-3-fluorophenyl)-2,5-dimethylpiperazine-1-carboxanilide

HRID 1838255Notes

Reaction equation

HRID 1838255 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([Br:9])[CH:6]=[CH:5][C:3]=1[NH2:4].ClC(Cl)(O[C:14](=[O:20])OC(Cl)(Cl)Cl)Cl.[CH3:22][C@H:23]1[CH2:28][NH:27][C@H:26]([CH3:29])[CH2:25][N:24]1[C:30]1[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([F:38])[CH:31]=1.C(N(CC)CC)C>C1COCC1>[Br:1][C:2]1[CH:8]=[C:7]([Br:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:14]([N:27]1[CH2:28][C@@H:23]([CH3:22])[N:24]([C:30]2[CH:37]=[CH:36][C:33]([C:34]#[N:35])=[C:32]([F:38])[CH:31]=2)[CH2:25][C@@H:26]1[CH3:29])=[O:20]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 120042,4-DibromoanilineHCID 94429TriphosgeneHCID 686909784-[(2S,5R)-2,5-Dimethylpiperazin-1-yl]-2-fluorobenzonitrile

Product 1

HCID 9849212trans-2',4'-Dibromo-4-(4-cyano-3-fluorophenyl)-2,5-dimethylpiperazine-1-carboxanilide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 300 mg portion of 2,4-dibromoaniline was dissolved in 10 ml of THF, and the solution was mixed with 153 mg of triphosgene under ice-cooling and then stirred at room temperature for 4 hours. Next, to this was added dropwise 5 ml of THF solution containing 427 mg of trans-4-(2,5-dimethylpiperazin-1-yl)-2-fluorobenzonitrile synthesized in Reference Example 1-1 and 460 mg of triethylamine, and the mixture was further stirred for 1 hour. After evaporation of the solvent, the thus obtained residue was dissolved in ethyl acetate, washed with saturated sodium bicarbonate solution and saturated brine in that order and then dried over sodium sulfate. After evaporation of the solvent under reduced pressure, the residue was purified by a silica gel column chromatography to obtain 390 mg of the title compound from chloroform-hexane (1:1, v/v) eluate as a light yellow product.

Workup

  1. temperaturecooling
  2. stirringthe mixture was further stirred for 1 hour
  3. customAfter evaporation of the solvent
  4. dissolutionthe thus obtained residue was dissolved in ethyl acetate
  5. washwashed with saturated sodium bicarbonate solution and saturated brine in that order
  6. dry with materialdried over sodium sulfate
  7. customAfter evaporation of the solvent under reduced pressure
  8. customthe residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-d6f8fbe2698c4bf5b80d2198f4088e10
Source dataset
uspto-grants-2004_01
Patent number
US06673799B1

Reaction notes

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