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

HRID 13790

반응식

HRID 13790 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-291c8fd6ca4843e6aa1a19535b164cd3
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728131B2

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