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 552860ノート

反応式

HRID 552860 の反応式
[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

参加物

4

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-404d61a3b51449b48064bad51edbfed7
出典データセット
uspto-grants-2011_05
特許番号
US07951825B2

反応ノート

読み込み中…