Trimethylsilyl cyanide → 2-(4-(7-(4-Chlorophenyl)-3-oxo-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)phenyl)-2-hydroxyacetonitrile

HRID 2101308

反応式

HRID 2101308 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:28])[N:15]([CH2:17][C:18]4[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:29]2[CH:36]=[CH:35][C:32]([CH:33]=[O:34])=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.[C:37]([Si](C)(C)C)#[N:38]>ClCCl.O.[Zn+2].[I-].[I-]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:28])[N:15]([CH2:17][C:18]4[CH:19]=[N:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:29]2[CH:30]=[CH:31][C:32]([CH:33]([OH:34])[C:37]#[N:38])=[CH:35][CH:36]=2)=[CH:4][CH:3]=1

参加物

6

反応物 2

HCID 82115Trimethylsilyl cyanideHCID 577994634-(7-(4-Chlorophenyl)-3-oxo-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)benzaldehyde

生成物 1

HCID 160051972-(4-(7-(4-Chlorophenyl)-3-oxo-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)phenyl)-2-hydroxyacetonitrile

試薬・触媒・溶媒 3

HCID 9883512zinc(II)iodide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of 4-(7-(4-chlorophenyl)-3-oxo-2-((6-(trifluoromethyl)pyridin-3-yl)methyl)-2,3-dihydro-[1,2,4]triazolo[4,3-a]pyridin-8-yl)benzaldehyde (38.0 mg, 0.075 mmol) in dichloromethane (1 mL) at room temperature under argon was added cyanotrimethylsilane (9.3 mg, 0.093 mmol) and then ZnI2 (2.4 mg, 0.0075 mmol). After 70 h, the reaction mixture was diluted with water and extracted twice with dichloromethane. The organic extracts were combined, dried (MgSO4), filtered and evaporated. Purification by preparative reverse phase HPLC (methanol-water-trifluoroacetic acid), pooling the fractions, evaporating, redissolving the residuum in dichloromethane, washing with saturated aq. NaHCO3 solution, drying (MgSO4), filtering and evaporating provided the title compound as a light yellow solid, 10.4 mg, 26%. HPLC/MS: retention time=3.56 min, [M+H]+=536. 1H NMR (CDCl3): δ 8.71 (d, J=1.7 Hz, 1H), 7.85 (dd, J=1.6 Hz, 7.7 Hz, 1H), 7.61 (d, J=8.3 Hz, 1H), 7.39 (d, J=8.3 Hz, 1H), 7.24 (d, J=6.5 Hz, 1H), 7.17 (d, J=8.3 Hz, 2H), 7.04 (d, J=8.3 Hz, 2H), 6.95 (d, J=6.6 Hz, 2H), 6.60 (d, J=7.2 Hz, 1H), 5.37 (s, 1H), 5.18 (s, 1H), 3.30 (br s, 1H).

後処理

  1. extractionextracted twice with dichloromethane
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customPurification by preparative reverse phase HPLC (methanol-water-trifluoroacetic acid)
  6. customevaporating
  7. dissolutionredissolving the residuum in dichloromethane
  8. washwashing with saturated aq. NaHCO3 solution
  9. dry with materialdrying (MgSO4)
  10. filtrationfiltering
  11. customevaporating

出典と根拠

ORDレコード
ord-e6550d29c7d04186934921e8cd1d643e
出典データセット
uspto-grants-2009_08
特許番号
US07572808B2

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