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Potassium Carbonate → 2-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]benzo[d]oxazole

HRID 710185
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HRID 710185 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=3[F:20])=[N:7][C:6]=2[CH:21]=1.Cl.[CH:23]([C:26]1[N:30]=[C:29]([CH:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[O:28][N:27]=1)([CH3:25])[CH3:24].C([O-])([O-])=O.[K+].[K+].C(CC(=O)C)(=O)C>CN1C(=O)CCC1.Cl[Cu]>[F:20][C:11]1[CH:12]=[C:13]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:14]=[CH:15][C:10]=1[C:8]1[O:9][C:5]2[CH:4]=[CH:3][C:2]([N:34]3[CH2:33][CH2:32][CH:31]([C:29]4[O:28][N:27]=[C:26]([CH:23]([CH3:25])[CH3:24])[N:30]=4)[CH2:36][CH2:35]3)=[CH:21][C:6]=2[N:7]=1
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참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 31261AcetylacetoneHCID 534008274-(3-Isopropyl-1,2,4-oxadiazol-5-YL)piperidine hydrochlorideHCID 712573645-Bromo-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

생성물 1

HCID 712574842-[2-Fluoro-4-(methylsulfonyl)phenyl]-5-[4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]benzo[d]oxazole수율 12.6%

시약·촉매·용매 2

HCID 62652Cuprous chloride촉매HCID 13387N-methyl-2-pyrrolidone용매

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온도
130 °C

실험 절차

Intermediate 28 (150 mg, 0.41 mmol), 3-isopropyl-5-(piperidin-4-yl)-1,2,4-oxadiazole hydrochloride (96 mg, 0.5 mmol), K2CO3 (59 mg, 0.43 mmol), CuCl (2 mg, 0.02 mmol), acetyl acetone (5 mg, 0.05 mmol) were dissolved in NMP (1 ml). This reaction mixture was stirred at 130° C. for 16 h under N2 atmosphere. Work up (EtOAc/H2O) followed by purification on combiflash using a gradient mixture of EtOAc and Petether (30:70) as eluent afforded the titled compound (25 mg) as a pale-yellow solid. M. P.: 206-209° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.26 (d, J 8.2, 1H), 7.97 (d, J 1.4, 1H), 7.69 (d, J 1.4, 1H), 7.63 (dd, J 1.5, 8.2, 1H), 7.56-7.48 (m, 2H), 3.49-3.39 (m, 2H), 3.15-3.04 (m, 5H), 3.03-2.93 (m, 2H), 2.25-2.16 (m, 4h), 1.36 (d, J 7, 6H).

후처리

  1. customWork up (EtOAc/H2O) followed by purification on combiflash
  2. additiona gradient mixture of EtOAc and Petether (30:70) as eluent

출처 및 근거

ORD 기록
ord-16c83d8eeaed415eb577f8855972b3ad
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09181214B2

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