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 2244650노트

반응식

HRID 2244650 반응식
[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

참가 물질

4

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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) and HOBt (65 mg) in DMF (1.5 ml) was added EDCI/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.

후처리

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

출처 및 근거

ORD 기록
ord-61b0e999b3304a568824535a085ece6e
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07678820B2

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