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Diisopropylethylamine → N-[1-(4-fluorophenyl)-5-methylpyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide

HRID 1754356
ノート
印刷プレビュー

反応式

HRID 1754356 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([NH2:14])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:15][C:16]1[N:17]([CH:25]([CH3:29])[C:26](O)=[O:27])[CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:20]=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>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH3:13])=[C:11]([NH:14][C:26](=[O:27])[CH:25]([N:17]3[CH:18]=[C:19]([C:21]([F:22])([F:24])[F:23])[N:20]=[C:16]3[CH3:15])[CH3:29])[CH:10]=[N:9]2)=[CH:6][CH:7]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 608668381-(4-fluorophenyl)-5-methyl-1H-pyrazol-4-amineHCID 867116772-[2-Methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid

生成物 1

HCID 76902772
N-[1-(4-fluorophenyl)-5-methylpyrazol-4-yl]-2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanamide
収率 24%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 1-(4-fluorophenyl)-5-methylpyrazol-4-amine (0.03 g, 0.16 mmol) in DMF (1.0 mL) was added 2-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propanoic acid (0.035 g, 0.16 mmol), followed by diisopropylethylamine (0.042 g, 0.32 mmol) and HATU (0.067 g, 0.18 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 (0.015 g, 0.038 mmol, 24%). 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.93 (s, 1H), 7.81 (d, J=1.3 Hz, 1H), 7.42-7.32 (m, 2H), 7.24-7.14 (m, 2H), 5.35 (q, J=6.8 Hz, 1H), 2.48 (s, 3H), 2.19 (s, 3H), 1.86 (d, J=7.0 Hz, 3H); MS: (ES) m/z calculated for C18H17F4N5O [M+H]+ 396.1, found 396.1.

後処理

  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)

出典と根拠

ORDレコード
ord-ab260a03d8a54b6e9422682b77c6d24f
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09169248B2

反応ノート

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