1,4-Dioxane hydrochloride → N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide hydrochloride

HRID 552860Notes

Reaction equation

HRID 552860 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][C:9](=[O:42])[CH2:10][N:11]1[C:19]2[C:14](=[C:15]([C:20]3[N:24]=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH:32]([CH3:37])[C:33]([F:36])([F:35])[F:34])=[C:27]([C:38]([F:41])([F:40])[F:39])[CH:26]=4)[O:22][N:21]=3)[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1.[ClH:43].O1CCOCC1>C(Cl)Cl>[ClH:43].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][C:9](=[O:42])[CH2:10][N:11]1[C:19]2[C:14](=[C:15]([C:20]3[N:24]=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH:32]([CH3:37])[C:33]([F:36])([F:34])[F:35])=[C:27]([C:38]([F:39])([F:40])[F:41])[CH:26]=4)[O:22][N:21]=3)[CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 59214364N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide

Product 1

HCID 86628813N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetic acid (150 mg) a HOBt(65 mg) in DMF (1.5 ml) was added EDCl/HCl (69 mg) at 0° C., followed by stirring at room temperature for 1 hour. After cooling to 0° C. again, 1-pyridin-2-ylmethanamine (39 mg) was added thereto, followed by stirring at room temperature for 15 hours. To the reaction solution was added a saturated aqueous NaHCO3 solution to complete the reaction. It was extracted with EtOAc, the organic layer was washed with saturated brine, dried over anhydrous MgSO4, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:CH3OH=100:0 to 95:5) to obtain N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide (157.8 mg) as a white solid. To a solution of N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide (120 mg) in methylene chloride (2.4 ml) was added dropwise 10 equivalents of 4M HCl/dioxane, followed by stirring for 1 hour. The reaction mixture was concentrated under reduced pressure, and powdered/washed with IPE. The obtained solid was collected by filtration, and dried to obtain N-(pyridin-2-ylmethyl)-2-(4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indol-1-yl)acetamide hydrochloride (126 mg) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washpowdered/washed with IPE
  3. filtrationThe obtained solid was collected by filtration
  4. customdried

Sources & evidence

ORD record
ord-404d61a3b51449b48064bad51edbfed7
Source dataset
uspto-grants-2011_05
Patent number
US07951825B2

Reaction notes

Loading…