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

HRID 1593391ノート

反応式

HRID 1593391 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5ac714e1c10f46f4aa542daedd5d89c1
出典データセット
uspto-grants-2007_11
特許番号
US07297698B2

反応ノート

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