4-Methylmorpholine → 1-{4-[5-(2-Fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester

HRID 2407508ノート

反応式

HRID 2407508 の反応式
ClC(OCC(C)C)=O.[CH2:9]([O:16][C:17]([C:19]1([C:50]([OH:52])=O)[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[N:36]=[C:35]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)=[C:39]([F:49])[CH:38]=4)[O:34][N:33]=3)=[CH:28][CH:27]=2)[CH2:21][CH2:20]1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[NH2:60][N:61]1[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1>O1CCCC1.O>[CH2:9]([O:16][C:17]([C:19]1([C:50](=[O:52])[NH:60][N:61]2[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]2)[CH2:20][CH2:21][N:22]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[N:36]=[C:35]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=5)=[C:39]([F:49])[CH:38]=4)[O:34][N:33]=3)=[CH:30][CH:31]=2)[CH2:23][CH2:24]1)=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 166581-AminopiperidineHCID 62365Isobutyl chloroformateHCID 595094311-{4-[5-(2-Fluorobiphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]benzyl}piperidine-4,4-dicarboxylic acid benzyl ester

生成物 1

HCID 595094951-{4-[5-(2-Fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
5 °C

実験手順

Isobutyl chloroformate (0.158 mL, 0.0012 mol) is added to a solution of 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-piperidine-4,4-dicarboxylic acid benzyl ester (0.6 g, 0.0010 mol) and N-methyl morpholine (0.156 mL, 0.0015 mol) in tetrahydrofuran (20 mL) at 5° C. The reaction mixture is stirred at 5° C. for 45 minutes. 1-Amino piperidine (0.162 mL, 0.0015 mol) is added to the reaction mixture and is stirred for 30 minutes at 5° C. and then at room temperature for 45 minutes. Demineralized water (10 mL) is added to the reaction mixture, Organic layer is separated and dried over sodium sulphate. Removal of solvent under reduced pressure gives a viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, hexane:ethyl acetate 70:30) to get 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester.

後処理

  1. stirringis stirred for 30 minutes at 5° C.
  2. waitat room temperature for 45 minutes
  3. customis separated
  4. dry with materialdried over sodium sulphate
  5. customRemoval of solvent under reduced pressure
  6. customgives a viscous liquid, which
  7. customis purified by column chromatography (silica gel 230-400 mesh, hexane:ethyl acetate 70:30)

出典と根拠

ORDレコード
ord-4964272338a64de49a43c0ee7b437a3a
出典データセット
uspto-grants-2014_08
特許番号
US08809539B2

反応ノート

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