Acetic Acid → 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium 2,2,2-trifluoroacetate

HRID 1475187Notes

Reaction equation

HRID 1475187 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([N:14]3[CH2:19][CH2:18][N:17](C(OCC4C=CC=CC=4)=O)[CH2:16][CH2:15]3)[CH:9]=2)[N:5]=[C:4]([C:30]2[O:34][N:33]=[C:32]([C:35]3[CH:40]=[CH:39][C:38]([O:41][C:42]([F:45])([F:44])[F:43])=[CH:37][CH:36]=3)[N:31]=2)[N:3]=1.C[C:47]([OH:49])=[O:48]>Br>[F:45][C:42]([F:43])([F:44])[C:47]([O-:49])=[O:48].[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([N:14]3[CH2:19][CH2:18][NH2+:17][CH2:16][CH2:15]3)[CH:9]=2)[N:5]=[C:4]([C:30]2[O:34][N:33]=[C:32]([C:35]3[CH:36]=[CH:37][C:38]([O:41][C:42]([F:45])([F:43])[F:44])=[CH:39][CH:40]=3)[N:31]=2)[N:3]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 86711878benzyl 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 867118804-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium 2,2,2-trifluoroacetateYield 84%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of benzyl 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate (200 mg, 0.30 mmol) in AcOH (1 mL), HBr (2 mL, 48% in H2O) was added at RT. The mixture was stirred at 40° C. for 1 h, and then concentrated under reduced pressure to give the crude product, which was purified by prep-HPLC (Mobile phase: A=0.01% TFA/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge C18, 5 um, 30 mm×150 mm) to afford 4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazin-1-ium 2,2,2-trifluoroacetate as a white solid (130 mg, 84%). MS (ES+) C22H21F3N8O2 requires: 486. found: 487 [M+H]+; 1H NMR (500 MHz, DMSO-d6) δ 8.98 (s, 2H), 8.22 (d, J=8.5 Hz, 2H), 8.15 (d, J=5.0 Hz, 1H), 7.61 (d, J=8.5 Hz, 2H), 6.87 (s, 1H), 6.57 (d, J=5.0 Hz, 1H), 5.54 (s, 2H), 3.73-3.71 (m, 4H), 3.22-3.19 (m, 4H), 2.59 (s, 3H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customto give the crude product, which
  3. customwas purified by prep-HPLC (Mobile phase
  4. waitGradient: B=60%-95% in 18 min

Sources & evidence

ORD record
ord-5a16de496808471c85e036f14c6f62da
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

Loading…