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

Reaktionsgleichung

Reaktionsgleichung von HRID 2101308
[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

Komponenten

6

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9883512zinc(II)iodideKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e6550d29c7d04186934921e8cd1d643e
Quelldatensatz
uspto-grants-2009_08
Patentnummer
US07572808B2

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