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

HRID 710187
ノート
印刷プレビュー

反応式

HRID 710187 の反応式
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
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 62652
Cuprous chloride
触媒
HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
130 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-822dccb9c2594164b03868d58c5ea5bb
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09181214B2

反応ノート

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