Cesium carbonate → 3-(4-(tert-butyl)phenyl)-5-(1-((2-chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole

HRID 1475207Notes

Reaction equation

HRID 1475207 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[N:20]=[C:19]([CH3:21])[NH:18][N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[Cl:28][C:29]1[CH:34]=[C:33]([CH2:35]Cl)[CH:32]=[CH:31][N:30]=1>CN(C=O)C>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[N:15]=[C:14]([C:16]3[N:20]=[C:19]([CH3:21])[N:18]([CH2:35][C:33]4[CH:32]=[CH:31][N:30]=[C:29]([Cl:28])[CH:34]=4)[N:17]=3)[O:13][N:12]=2)=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 111265732-Chloro-4-(chloromethyl)pyridineHCID 867118993-(4-(tert-butyl)phenyl)-5-(5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole

Product 1

HCID 867119003-(4-(tert-butyl)phenyl)-5-(1-((2-chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazoleYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-(tert-Butyl)phenyl)-5-(5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole (140 mg, 0.495 mmol) was placed in DMF (10 mL) and Cs2CO3 (193 mg, 0.594 mmol) was added. The reaction was stirred for 5 min and 2-chloro-4-(chloromethyl)pyridine (96 mg, 0.594 mmol) was added. The reaction was stirred at 45° C. overnight and was then partitioned between H2O (25 mL) and EtOAc (25 mL). The organic layer was separated, washed with H2O (2×25 mL) and brine (15 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product which was purified by silica gel chromatography (EtOAc/Hexane 0%-100% EtOAc) to afford 3-(4-(tert-butyl)phenyl)-5-(1-((2-chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole as a yellow solid (90 mg, 45%). MS (ES+) C21H21ClN6O requires: 408. found 409 [M+H]+; 1H NMR (600 MHz, CDCl3) δ 8.42 (d, J=5.2 Hz, 1H), 8.16 (d, J=8.5 Hz, 2H), 7.52 (d, J=8.5 Hz, 2H), 7.16 (s, 1H), 7.05 (d, J=5.2 Hz, 1H), 5.46 (s, 2H), 2.57 (s, 3H), 1.37 (s, 9H).

Workup

  1. stirringThe reaction was stirred at 45° C. overnight
  2. customwas then partitioned between H2O (25 mL) and EtOAc (25 mL)
  3. customThe organic layer was separated
  4. washwashed with H2O (2×25 mL) and brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the crude product which
  9. customwas purified by silica gel chromatography (EtOAc/Hexane 0%-100% EtOAc)

Sources & evidence

ORD record
ord-c90664394c3c4c11a8644d17cd8b7b76
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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