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

반응식

HRID 2101308 반응식
[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

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 3

HCID 9883512zinc(II)iodide촉매HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-e6550d29c7d04186934921e8cd1d643e
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07572808B2

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