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 2407508노트

반응식

HRID 2407508 반응식
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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
5 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-4964272338a64de49a43c0ee7b437a3a
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809539B2

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