Diisopropylethylamine → [8-(3,5-Bis-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[3-fluoro-1-(5-methyl-[1,3,4]oxadiazol-2-yl)-piperidin-4-yl]-amine

HRID 451578Notes

Reaction equation

[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C:13]2[C:14]3[N:15]([N:19]=[C:20]([NH:22][CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH:24]4[F:29])[N:21]=3)[CH:16]=[CH:17][CH:18]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Br[C:33]1[O:34][C:35]([CH3:38])=[N:36][N:37]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([C:13]2[C:14]3[N:15]([N:19]=[C:20]([NH:22][CH:23]4[CH2:28][CH2:27][N:26]([C:33]5[O:34][C:35]([CH3:38])=[N:36][N:37]=5)[CH2:25][CH:24]4[F:29])[N:21]=3)[CH:16]=[CH:17][CH:18]=2)[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 8-(3,5-bis(trifluoromethyl)phenyl)-N-(3-fluoropiperidin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (example 269b, 68 mg, 152 μmol), 2-bromo-5-methyl-1,3,4-oxadiazole (32.2 mg, 198 μmol) and diisopropylethylamine (39.3 mg, 53.1 μL, 304 μmol) dissolved in dry dioxane (2 mL) was stirred at 70° C. for 12 hours and then at 110° C. for 1 hour. Further diisopropylethylamine (39.3 mg, 53.1 μL, 304 μmol) and 2-bromo-5-methyl-1,3,4-oxadiazole (32.2 mg, 198 μmol) were added and heated to 110° C. for another hour. The solvent was evaporated and the residue directly purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane). The title compound was obtained as colorless oil (46 mg, 57%) as a mixture of cis- and trans-isomers.

Workup

waitat 110° C. for 1 hour
temperatureheated to 110° C. for another hour
customThe solvent was evaporated
customthe residue directly purified by flash chromatography (silica gel, 70 g, 0% to 15% MeOH/NH4OH (9:1) in dichloromethane)

Sources & evidence

ORD record: ord-25a1c3b42efa4625b766aa65d4933da3
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486967B2

Reaction notes

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