Diisopropylethylamine → 1-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

HRID 1993711ノート

反応式

HRID 1993711 の反応式
CCN(C(C)C)C(C)C.[NH2:10][C:11]1[CH:12]=[C:13]([CH3:33])[C:14]([N:17]2[CH2:22][CH2:21][N:20]([C:23]([C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])=[O:24])[CH2:19][CH2:18]2)=[N:15][CH:16]=1.ClC(Cl)(Cl)C[O:37][C:38](=O)[NH:39][C:40]1[N:41]([C:50]2[CH:55]=[CH:54][C:53]([CH3:56])=[CH:52][CH:51]=2)[N:42]=[C:43]([C:45]([CH3:49])([CH3:48])[CH2:46][F:47])[CH:44]=1>C(#N)C>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[C:23]([N:20]1[CH2:19][CH2:18][N:17]([C:14]2[N:15]=[CH:16][C:11]([NH:10][C:38]([NH:39][C:40]3[N:41]([C:50]4[CH:55]=[CH:54][C:53]([CH3:56])=[CH:52][CH:51]=4)[N:42]=[C:43]([C:45]([CH3:49])([CH3:48])[CH2:46][F:47])[CH:44]=3)=[O:37])=[CH:12][C:13]=2[CH3:33])[CH2:22][CH2:21]1)=[O:24]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 68540113[4-(5-Amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanoneHCID 68540645[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

生成物 1

HCID 591344441-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea収率 48%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
80 °C

実験手順

Add DIEA (2 equiv.) to a solution of [4-(5-amino-3-methyl-pyridin-2-yl)-piperazin-1-yl]-(2,6-difluoro-phenyl)-methanone (400 mg, 1.205 mmol) and [5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (1 equiv) in acetonitrile (12 mL). Stir the mixture at 80° C. in a sealed tube. After 4 days, remove solvent. Dilute crude with DCM, extract with water, and dry over Na2SO4. Filter and remove solvent under reduced pressure. Subject solid to silica gel chromatography, eluting with hexane/acetone 3:1 to obtain 352 mg of 1-{6-[4-(2,6-difluoro-benzoyl)-piperazin-1-yl]-5-methyl-pyridin-3-yl}-3-[5-(2-fluoro-1,1-dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea as a white solid (48% yield). ES+(m/z): 606 [M+1]

後処理

  1. customremove solvent
  2. additionDilute crude with DCM
  3. extractionextract with water
  4. dry with materialdry over Na2SO4
  5. filtrationFilter
  6. customremove solvent under reduced pressure
  7. washeluting with hexane/acetone 3:1

出典と根拠

ORDレコード
ord-886edfdb7d06477dbad84e8ce2b560c5
出典データセット
uspto-grants-2010_01
特許番号
US07652015B2

反応ノート

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