1-Methylpiperazine → 3-(4-(tert-butyl)phenyl)-5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl)methyl)-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole

HRID 1475208Notes

Reaction equation

HRID 1475208 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])[N:18]([CH2:22][C:23]4[CH:28]=[CH:27][N:26]=[C:25](Cl)[CH:24]=4)[N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1>CS(C)=O>[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])[N:18]([CH2:22][C:23]4[CH:28]=[CH:27][N:26]=[C:25]([N:34]5[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]5)[CH:24]=4)[N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 867119003-(4-(tert-butyl)phenyl)-5-(1-((2-chloropyridin-4-yl)methyl)-5-methyl-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole

Product 1

HCID 867119013-(4-(tert-butyl)phenyl)-5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl)methyl)-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazoleYield 22%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
140 °C

Procedure

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 (90 mg, 0.221 mmol) and 1-methylpiperazine (265 mg, 2.65 mmol) were dissolved in DMSO (3 mL) in a sealed tube reaction vessel. The reaction was heated at 140° C. overnight and then cooled to RT and 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 prep-HPLC (MeCN/H2O 20%-60% MeCN, containing 0.1% TFA). The product was taken up in EtOAc (10 mL), washed with sat. NaHCO3 (10 mL), dried over Na2SO4, filtered, and concentrated to afford 3-(4-(tert-butyl)phenyl)-5-(5-methyl-1-((2-(4-methylpiperazin-1-yl)pyridin-4-yl)methyl)-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazole as a yellow foam (23 mg, 22%). MS (ES+) C26H32N8O requires: 472. found 473 [M+H]+; 1H NMR (600 MHz, CDCl3) δ 8.19-8.15 (m, 3H), 7.51 (d, J=8.4 Hz, 2H), 6.42 (d, J=4.9 Hz, 1H), 6.39 (s, 1H), 5.36 (s, 2H), 3.70-3.50 (m, 4H), 2.69-2.46 (bs, 3H), 2.54 (s, 3H), 2.46-2.30 (m, 4H), 1.37 (s, 9H).

Workup

  1. temperaturecooled to RT
  2. custompartitioned 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 prep-HPLC (MeCN/H2O 20%-60% MeCN, containing 0.1% TFA)
  10. washwashed with sat. NaHCO3 (10 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-21b5796988d54af99b768c615d152476
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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