Toluene → (2R,5S)-4-(4-Cyano-3-fluoro-5-methoxyphenyl)-N-(2-cyclopropylpyrimidine-5-yl)-2,5-dimethylpiperazine-1-carboxamide

HRID 1445479Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1445479
[N-:1]=[N+]=[N-].C1(C)C=CC=CC=1.[CH:11]1([C:14]2C=[CH:18][C:17]([N:20]=[C:21]=[O:22])=[CH:16][N:15]=2)[CH2:13][CH2:12]1.[CH3:23][C@H:24]1[CH2:29][NH:28][C@H:27]([CH3:30])[CH2:26][N:25]1[C:31]1[CH:38]=[C:37]([O:39][CH3:40])[C:34]([C:35]#[N:36])=[C:33]([F:41])[CH:32]=1>C(OCC)(=O)C>[C:35]([C:34]1[C:37]([O:39][CH3:40])=[CH:38][C:31]([N:25]2[C@@H:24]([CH3:23])[CH2:29][N:28]([C:21]([NH:20][C:17]3[CH:18]=[N:1][C:14]([CH:11]4[CH2:12][CH2:13]4)=[N:15][CH:16]=3)=[O:22])[C@H:27]([CH3:30])[CH2:26]2)=[CH:32][C:33]=1[F:41])#[N:36]

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 33558Azide2×HCID 230820322-Cyclopropyl-5-isocyanatopyridineHCID 686911704-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-2-fluoro-6-methoxybenzonitrile

Produkt 1

HCID 68690780(2R,5S)-4-(4-Cyano-3-fluoro-5-methoxyphenyl)-N-(2-cyclopropylpyrimidine-5-yl)-2,5-dimethylpiperazine-1-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Into 10 ml of ethyl acetate was suspended 374 mg of 2-cyclopropylpyrimidine-5-carboxylic acid, and then 345 mg of triethylamine and 690 mg of DPPA were added thereto, followed by 2 hours of stirring at room temperature. The reaction 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. Toluene was added thereto and the solvent was removed by evaporation to obtain 2-cyclopropylpyrimidine-5-carboxyl azide. The resulting acid azide was dissolved into 20 ml of toluene and the solution was heated and refluxed for 30 minutes to convert the acid azide into 2-cyclopropyl-5-isocyanatopyridine, followed by ice-cooling of the reaction solution. Into 3 ml of ethyl acetate was dissolved 500 mg of 4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-2-fluoro-6-methoxybenzonitrile, and the resulting solution was added dropwise to the above reaction solution, followed by 18 hours of stirring at room temperature. The reaction solution was evaporated and the resulting residue was subjected to silica gel column chromatography and a resulting oily product from an eluate using methanol-chloroform (3:97, v/v) was crystallized from ethyl acetate-diethyl ether to obtain 626 mg of the title compound.

Aufarbeitung

  1. temperaturethe solution was heated
  2. temperaturerefluxed for 30 minutes
  3. temperaturecooling of the reaction solution
  4. additionthe resulting solution was added dropwise to the above reaction solution
  5. customThe reaction solution was evaporated
  6. customwas crystallized from ethyl acetate-diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-f76af8f63c6b432a80aa0bbfa599a01e
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07666873B2

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