Diisopropylethylamine → 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-N-(6-(trifluoromethyl) pyridin-3-yl)-1H-indazole-3-carboxamide

HRID 2367702ノート

反応式

HRID 2367702 の反応式
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Br:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1)[N:30]=[C:29]2[C:41]([OH:43])=O.C(N(C(C)C)CC)(C)C.[NH2:53][C:54]1[CH:55]=[CH:56][C:57]([C:60]([F:63])([F:62])[F:61])=[N:58][CH:59]=1>CN(C=O)C>[Br:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[N:31]([CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1)[N:30]=[C:29]2[C:41]([NH:53][C:54]1[CH:59]=[N:58][C:57]([C:60]([F:63])([F:61])[F:62])=[CH:56][CH:55]=1)=[O:43]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 698056555-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid

生成物 1

HCID 866796985-bromo-1-(tetrahydro-2H-pyran-2-yl)-N-(6-(trifluoromethyl) pyridin-3-yl)-1H-indazole-3-carboxamide収率 93%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

HATU (1.125 g, 2.96 mmol) was added to a solution of 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (CXVIII) (0.876 g, 2.69 mmol) and diisopropylethylamine (1.03 mL, 5.92 mmol) in DMF stirred at room temperature under argon. After stirring 5 min, the solution was added with 5-amino-2-trifluoromethylpyridine (CXXVII) (0.479 g, 2.96 mmol). The solution was stirred 24 h at room temperature under argon. The DMF was removed under reduced pressure, and the residue was treated with water, sonicated briefly and filtered. The solids were washed with cold water and dried at room temperature. The product was purified by silica gel column chromatography (100% hexanes→7:93 EtOAc:hexanes) to afford 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-N-(6-(trifluoromethyl)pyridin-3-yl)-1H-indazole-3-carboxamide (CXXVIII) as a white solid (1.17 g, 2.50 mmol, 93% yield). 1H NMR (DMSO-d6) δ ppm 10.93 (s, 1H), 9.23 (d, J=1.9 Hz, 1H), 8.60 (dd, J=6.8, 1.4 Hz, 1H), 8.38 (d, J=4.4 Hz, 1H), 7.95 (m, 2H), 7.70 (dd, J=7.1, 1.5 Hz, 1H), 6.04 (dd, J=8.1, 1.9 Hz, 1H), 3.98 (m, 1H), 3.82 (m, 1H), 2.59-2.54 (m, 1H), 2.08-2.03 (m, 2H), 1.81-1.77 (m, 1H). 1.66-1.61 (m, 2H); ESIMS found for C19H16BrF3N4O2 m/z 470.0 (M+H).

後処理

  1. stirringAfter stirring 5 min
  2. stirringThe solution was stirred 24 h at room temperature under argon
  3. customThe DMF was removed under reduced pressure
  4. additionthe residue was treated with water
  5. customsonicated briefly
  6. filtrationfiltered
  7. washThe solids were washed with cold water
  8. customdried at room temperature
  9. customThe product was purified by silica gel column chromatography (100% hexanes→7:93 EtOAc:hexanes)

出典と根拠

ORDレコード
ord-2c37d51f5b98495eae5d6c194484bc6a
出典データセット
uspto-grants-2014_04
特許番号
US08697887B2

反応ノート

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