benzyl 4-(4-((2-methyl-5-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-2H-1,2,4-triazol-3-yl)methyl)pyridin-2-yl)piperazine-1-carboxylate → 3-(4-(Trifluoromethoxy)phenyl)-1,2,4-oxadiazole formate salt

HRID 517565Notes

Reaction equation

CN1C(CC2C=CN=C(N3CCN([C:20]([O:22]CC4C=CC=CC=4)=[O:21])CC3)C=2)=NC([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)=N1>CC(O)=O.Br>[CH:20]([OH:22])=[O:21].[F:45][C:42]([F:43])([F:44])[O:41][C:38]1[CH:37]=[CH:36][C:35]([C:32]2[N:31]=[CH:30][O:34][N:33]=2)=[CH:40][CH:39]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of benzyl 4-(4-((2-methyl-5-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-2H-1,2,4-triazol-3-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 to give the crude product, which was purified by pre-HPLC (Mobile phase: A=0.01% HCOOH/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge (C18, 5 um, 30 mm*150 mm) to afford compound 5-(1-methyl-5-(2-(piperazin-1-yl)pyridin-4-yl)methyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole formate salt as a white solid (120 mg, 61%). MS (ES+) C22H21F3N8O2 requires: 486, found: 487[M+H]+; 1H NMR (500 MHz, DMSO-d6) δ ppm 8.32 (bs, 1H), 8.22 (d, J=8.5 Hz, 2H), 8.08 (d, J=5.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 6.81 (s, 1H), 6.58 (d, J=5.5 Hz, 1H), 4.27 (s, 2H), 4.00 (s, 3H), 3.6-3.48 (m, 4H), 2.99-2.85 (m, 4H).

Workup

concentrationconcentrated
customto give the crude product, which
customwas purified by pre-HPLC (Mobile phase
waitGradient: B=60%-95% in 18 min

Sources & evidence

ORD record: ord-88047f5c4e874259abc1a218a7fd2b49
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115120B2

Reaction notes

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