1H-1,2,4-Triazole → (3-((5-Methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)(4-methylpiperazin-1-yl)methanone

HRID 1475213Notes

Reaction equation

HRID 1475213 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[C:10]([CH:15]=[CH:16][CH:17]=2)[C:11]([O:13]C)=O)[N:5]=[C:4]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=3)[N:19]=2)[N:3]=1.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.N1C=NC=N1.C1CCN2C(=NCCC2)CC1>>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[C:10]([C:11]([N:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)=[O:13])[CH:15]=[CH:16][CH:17]=2)[N:5]=[C:4]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:24]=[CH:25][C:26]([O:29][C:30]([F:32])([F:31])[F:33])=[CH:27][CH:28]=3)[N:19]=2)[N:3]=1

Participants

5

Reactant 4

HCID 92571H-1,2,4-TriazoleHCID 531671-MethylpiperazineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86711907methyl 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)benzoate

Product 1

HCID 86711908(3-((5-Methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)(4-methylpiperazin-1-yl)methanoneYield 38%

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)benzoate (46 mg, 0.1 mmol) and 1-methylpiperazine (10 mg, 0.1 mmol) was treated with 1,2,4-triazole (1.4 mg, 0.02 mmol) and DBU (3 mg, 0.02 mmol)), and heated to 100° C. overnight. The crude product was purified by a silica gel column (MeOH/EtOAc 1% to 10% MeOH) to give (3-((5-Methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenyl)(4-methylpiperazin-1-yl)methanone as a yellow solid (20 mg, 38%). MS (ES+) C25H24F3N7O3 requires: 527. found: 528 [M+H]+. 1H NMR (600 MHz, CDCl3) δ8.28 (d, J=8.8 Hz, 2H), 7.43 (t, J=7.6 Hz, 1H), 7.39 (d, J=7.6 Hz, 1H), 7.35 (d, J=8.5 Hz, 2H), 7.32 (s, 1H), 7.29 (d, J=7.7 Hz, 1H), 5.48 (s, 2H), 3.82-3.74 (m, 2H), 3.42-3.36 (m, 2H), 2.57 (s, 3H), 2.51-2.44 (m, 2H), 2.35-2.30 (m, 2H), 2.29 (s, 3H).

Workup

  1. customThe crude product was purified by a silica gel column (MeOH/EtOAc 1% to 10% MeOH)

Sources & evidence

ORD record
ord-539b4135efea4ab59790d4fec87201b9
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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