1-(4-Aminophenyl)cyclopropanecarbonitrile → (2R,5S)-4'-(1-Cyanocyclopropyl)-4-(4-cyano-3-fluoro-5-methoxyphenyl)-2,5-dimethylpiperazine-1-carboxanilide

HRID 1445480Notes

Reaction equation

HRID 1445480 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:13](=O)(OC1C=CC=CC=1)[O:14]Cl.[CH3:24][C@H:25]1[CH2:30][NH:29][C@H:28]([CH3:31])[CH2:27][N:26]1[C:32]1[CH:39]=[C:38]([O:40][CH3:41])[C:35]([C:36]#[N:37])=[C:34]([F:42])[CH:33]=1>N1C=CC=CC=1>[C:11]([C:8]1([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:13]([N:29]3[CH2:30][C@H:25]([CH3:24])[N:26]([C:32]4[CH:39]=[C:38]([O:40][CH3:41])[C:35]([C:36]#[N:37])=[C:34]([F:42])[CH:33]=4)[CH2:27][C@H:28]3[CH3:31])=[O:14])=[CH:7][CH:6]=2)[CH2:9][CH2:10]1)#[N:12]

Participants

5

Reactant 3

HCID 138269361-(4-Aminophenyl)cyclopropanecarbonitrileHCID 20449549Chloro phenyl carbonateHCID 686911704-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-2-fluoro-6-methoxybenzonitrile

Product 1

HCID 68693988(2R,5S)-4'-(1-Cyanocyclopropyl)-4-(4-cyano-3-fluoro-5-methoxyphenyl)-2,5-dimethylpiperazine-1-carboxanilideYield 58.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

Into 10 ml of pyridine was dissolved 475 mg of 1-(4-aminophenyl)cyclopropanecarbonitrile, and then 493 mg of chloro phenyl carbonate was added thereto under ice-cooling, followed by 24 hours of stirring at room temperature. Then, 5 ml of a pyridine solution of 790 mg of 4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-2-fluoro-6-methoxybenzonitrile was added dropwise thereto, followed by 1 hour of stirring at 100° C. After the reaction solution was evaporated and the resulting residue was dissolved in ethyl acetate, the solution was washed with a saturated sodium bicarbonate aqueous solution and then water. After the solution was dried over anhydrous sodium sulfate, the solvent was removed by evaporation. The residue was subjected to silica gel column chromatography to obtain 751 mg of the title compound from an eluate using ethyl acetate-hexane (1:1, v/v).

Workup

  1. temperatureunder ice-cooling
  2. waitfollowed by 1 hour
  3. stirringof stirring at 100° C
  4. customAfter the reaction solution was evaporated
  5. dissolutionthe resulting residue was dissolved in ethyl acetate
  6. washthe solution was washed with a saturated sodium bicarbonate aqueous solution
  7. dry with materialAfter the solution was dried over anhydrous sodium sulfate
  8. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-02ced2c762d9449fa98edd92ca632761
Source dataset
uspto-grants-2010_02
Patent number
US07666873B2

Reaction notes

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