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Potassium Carbonate → 5-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

HRID 710187
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HRID 710187 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.[CH2:22]([N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+].C(CC(=O)C)(=O)C>CN1C(=O)CCC1.Cl[Cu]>[CH2:22]([N:29]1[CH2:34][CH2:33][N:32]([C:2]2[CH:3]=[CH:4][C:5]3[O:9][C:8]([C:10]4[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][C:11]=4[F:20])=[N:7][C:6]=3[CH:21]=2)[CH2:31][CH2:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
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참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 31261AcetylacetoneHCID 759941-BenzylpiperazineHCID 712573645-Bromo-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

생성물 1

HCID 712570875-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole수율 40.7%

시약·촉매·용매 2

HCID 62652
Cuprous chloride
촉매
HCID 13387N-methyl-2-pyrrolidone용매

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온도
130 °C

실험 절차

Intermediate 28 (490 mg, 1.32 mmol), N-Benzylpiprazine (280 mg, 1.6 mmol), K2CO3 (190 mg, 1.4 mmol), CuCl (6.5 mg, 0.05 mmol), acetyl acetone (17 mg, 0.12 mmol) were dissolved in NMP (2 ml). This reaction mixture was stirred at 130° C. for 15 h under N2 atmosphere. Work up (EtOAc/H2O) followed by column purification on 60-120 mesh silica gel using a gradient mixture of EtOAc and Petether (1:1) as eluent afforded 5-(4-benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (250 mg) as a yellow solid. 5-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole (130 mg, 0.28 mmol) dissolved in DCM (15 ml) and added isopropylchloro formate (102 mg, 0.84 mmol). This mixture was stirred at reflux for 18 h. Work up (DCM/H2O) followed by purification of the crude by column chromatography on 230-400 mesh silica gel 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.: 231-234° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 8.28 (d, J 8.7, 1H), 7.96 (d, J 1.6, 1H), 7.68-7.64 (m, 2H), 7.57-7.47 (m, 2H), 4.95 (septet, J 6.2, 1H), 3.71-3.63 (m, 4H), 3.12-3.06 (m, 4H), 1.26 (d, J 6.2, 6H).

후처리

  1. customWork up (EtOAc/H2O) followed by column purification on 60-120 mesh silica gel using
  2. additiona gradient mixture of EtOAc and Petether (1:1) as eluent

출처 및 근거

ORD 기록
ord-822dccb9c2594164b03868d58c5ea5bb
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09181214B2

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