三乙胺 → N-[1-(4-chlorophenyl)-5-isopropyltriazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide

HRID 1754380笔记

反应方程式

HRID 1754380 反应方程式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([NH2:16])[N:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:17][C:18]1[N:19]([CH:27]([CH3:31])[C:28](O)=[O:29])[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH:13]([CH3:14])[CH3:15])=[C:11]([NH:16][C:28](=[O:29])[CH:27]([N:19]3[CH:20]=[C:21]([C:23]([F:24])([F:26])[F:25])[N:22]=[C:18]3[CH3:17])[CH3:31])[N:10]=[N:9]2)=[CH:6][CH:7]=1

参与物

7

反应物 4

HCID 8471三乙胺HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 795018061-(4-Chlorophenyl)-5-isopropyltriazol-4-amineHCID 867116772-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid

产物 1

HCID 75593297N-[1-(4-chlorophenyl)-5-isopropyltriazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide收率 10%

试剂、催化剂与溶剂 2

HCID 6344二氯甲烷溶剂HCID 516892碳酸氢钠溶剂

实验过程

A mixture of 1-(4-chlorophenyl)-5-isopropyltriazol-4-amine (from step f, 0.025 g, 0.11 mmol), 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (0.031 g, 0.13 mmol), HATU (0.057 g, 0.13 mmol), and 100 μL of Et3N in 1 mL of CH2Cl2 was stirred at room temperature. After 30 minutes, the reaction mixture was diluted with 10 mL of aqueous saturated sodium bicarbonate and extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) provided the title compound as a colorless solid (0.0051 g, 0.011 mmol, 10%). 1H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 7.65 (s, 1H), 7.54 (d, J=8.3 Hz, 2H), 7.34 (d, J=8.3 Hz, 2H), 5.26 (q, J=7.4 Hz, 1H), 3.0-2.98 (m, 1H), 2.62 (s, 3H), 1.86 (d, J=7.4 Hz, 3H), 1.14 (t, J=6.4 Hz, 6H). MS: (ES) m/z calculated for C19H20ClF3N6O [M+H]+ 441.1, found 441.2.

后处理

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

来源与证据

ORD记录
ord-05174b6579764b6bbc253d1cf95ab152
来源数据集
uspto-grants-2015_10
专利号
US09169248B2

反应笔记

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