Diisopropylethylamine → 4-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethyl-N-{4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]phenyl}benzamide

HRID 13790

反応式

HRID 13790 の反応式
[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][C:12]=2[C:20]([F:23])([F:22])[F:21])[CH2:6][CH2:5]1.[I-].ClC1C=CC=C[N+]=1C.[CH3:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][C:35]=1[NH:41][C:42]1[N:47]=[C:46]([C:48]2[CH:49]=[N:50][CH:51]=[N:52][CH:53]=2)[CH:45]=[CH:44][N:43]=1.C(N(C(C)C)CC)(C)C>CN(C)C=O.O>[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH:38][C:37]3[CH:39]=[CH:40][C:34]([CH3:33])=[C:35]([NH:41][C:42]4[N:47]=[C:46]([C:48]5[CH:53]=[N:52][CH:51]=[N:50][CH:49]=5)[CH:45]=[CH:44][N:43]=4)[CH:36]=3)=[O:16])=[CH:13][C:12]=2[C:20]([F:23])([F:21])[F:22])[CH2:6][CH2:5]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 231458394-Methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]anilineHCID 231459454-[4-(2-Fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethylbenzoic acid

生成物 1

HCID 111576534-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethyl-N-{4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]phenyl}benzamide収率 55.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

Under an argon atmosphere, 1.71 g of 4-[4-(2-fluoroethyl)piperazin-1-ylmethyl]-3-trifluoromethylbenzoic acid (Reference Example 14) was dissolved in 14 ml of anhydrous N,N-dimethylformamide and 1.56 g of 2-chloro-1-methylpyridinium iodide was added, followed by stirring at room temperature for 10 minutes. 1.50 g of 4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]aniline (Reference Example 18) and 1.13 ml of N,N-diisopropyl-N-ethylamine were added in turn, followed by stirring at room temperature for 1 hour. 300 ml of water was added to the reaction solution, followed by extraction with ethyl acetate. Two hundred ml of saturated sodium hydrogen carbonate was added to the aqueous layer and the mixture was further extracted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography and the crude crystals were washed with diethyl ether-ethyl acetate to obtain 1.68 g of the objective compound as pale yellow crystals.

後処理

  1. stirringby stirring at room temperature for 1 hour
  2. extractionfollowed by extraction with ethyl acetate
  3. additionTwo hundred ml of saturated sodium hydrogen carbonate was added to the aqueous layer
  4. extractionthe mixture was further extracted with ethyl acetate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by column chromatography
  8. washthe crude crystals were washed with diethyl ether-ethyl acetate

出典と根拠

ORDレコード
ord-291c8fd6ca4843e6aa1a19535b164cd3
出典データセット
uspto-grants-2010_06
特許番号
US07728131B2

関連ノート

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