Water methylene chloride → Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperazine-1-carboxylate

HRID 710188ノート

反応式

HRID 710188 の反応式
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]3[O:21][C:20]([C:22]4[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=4[F:32])=[N:19][C:18]=3[CH:33]=2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(Cl)Cl.[OH2:37]>C(Cl)Cl>[F:32][C:23]1[CH:24]=[C:25]([S:28]([CH3:31])(=[O:29])=[O:30])[CH:26]=[CH:27][C:22]=1[C:20]1[O:21][C:17]2[CH:16]=[CH:15][C:14]([N:11]3[CH2:12][CH2:13][N:8]([C:1]([O:21][CH:17]([CH3:18])[CH3:16])=[O:37])[CH2:9][CH2:10]3)=[CH:33][C:18]=2[N:19]=1

参加物

4

反応物 2

HCID 21908982Water methylene chlorideHCID 712570875-(4-Benzylpiperazin-1-yl)-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole

生成物 1

HCID 71257301Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperazine-1-carboxylate

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

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. temperatureat reflux for 18 h
  2. customfollowed by purification of the crude by column chromatography on 230-400 mesh silica gel using
  3. additiona gradient mixture of EtOAc and Petether (30:70) as eluent

出典と根拠

ORDレコード
ord-64290fe5798a4e2891ac79da6a3db324
出典データセット
uspto-grants-2015_11
特許番号
US09181214B2

反応ノート

読み込み中…