N,N-二异丙基乙胺 → N-[5-tert-butyl-1-(4-fluorophenyl)pyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide

HRID 1754364笔记

反应方程式

HRID 1754364 反应方程式
[C:1]([C:5]1[N:9]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:8]=[CH:7][C:6]=1[NH2:17])([CH3:4])([CH3:3])[CH3:2].[CH3:18][C:19]1[N:20]([CH:28]([CH3:32])[C:29](O)=[O:30])[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[N:23]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[C:1]([C:5]1[N:9]([C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[N:8]=[CH:7][C:6]=1[NH:17][C:29](=[O:30])[CH:28]([N:20]1[CH:21]=[C:22]([C:24]([F:25])([F:27])[F:26])[N:23]=[C:19]1[CH3:18])[CH3:32])([CH3:4])([CH3:2])[CH3:3]

参与物

7

反应物 4

HCID 81531N,N-二异丙基乙胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867116772-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acidHCID 867243735-Tert-butyl-1-(4-fluorophenyl)pyrazol-4-amine

产物 1

HCID 86724372N-[5-tert-butyl-1-(4-fluorophenyl)pyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide收率 26.2%

试剂、催化剂与溶剂 2

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

To a solution of 5-tert-butyl-1-(4-fluorophenyl)pyrazol-4-amine (0.03 g, 0.13 mmol) in DMF (1.0 mL) was added 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (0.029 g, 0.13 mmol), followed by diisopropylethylamine (0.033 g, 0.26 mmol) and HATU (0.054 g, 0.14 mmol). After stirring at room temperature for 1 h, the reaction was diluted with water and the aqueous layer was extracted with ethyl acetate (2×5 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the title compound as a white solid (0.0145 g, 0.034 mmol, 25%). 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.45 (q, J=1.2 Hz, 1H), 7.33-7.24 (m, 2H), 7.16-7.07 (m, 2H), 6.89 (s, 1H), 4.90 (d, J=7.3 Hz, 1H), 2.47 (s, 3H), 1.86 (d, J=7.3 Hz, 3H), 1.11-1.03 (m, 9H); MS: (ES) m/z calculated for C21H23F4N5O [M+H]+ 438.2, found 438.0.

后处理

  1. extractionthe aqueous layer was extracted with ethyl acetate (2×5 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude product was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

来源与证据

ORD记录
ord-4a2cb83f476446dab354a91ee07b9311
来源数据集
uspto-grants-2015_10
专利号
US09169248B2

反应笔记

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