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

HRID 2407511노트

반응식

HRID 2407511 반응식
ON1C2C=CC=CC=2N=N1.[CH2:11]([O:18][C:19]([C:21]1([C:52]([OH:54])=O)[CH2:26][CH2:25][N:24]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]3[N:38]=[C:37]([C:39]4[CH:44]=[CH:43][C:42]([C:45]5[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=5)=[C:41]([F:51])[CH:40]=4)[O:36][N:35]=3)=[CH:30][CH:29]=2)[CH2:23][CH2:22]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH:55]1[CH2:60][CH2:59][O:58][CH2:57][CH2:56]1.Cl.CN(C)CCCN=C=NCC>O1CCCC1.O>[CH2:11]([O:18][C:19]([C:21]1([C:52]([N:55]2[CH2:60][CH2:59][O:58][CH2:57][CH2:56]2)=[O:54])[CH2:22][CH2:23][N:24]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([C:34]3[N:38]=[C:37]([C:39]4[CH:44]=[CH:43][C:42]([C:45]5[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=5)=[C:41]([F:51])[CH:40]=4)[O:36][N:35]=3)=[CH:32][CH:33]=2)[CH2:25][CH2:26]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

참가 물질

7

반응물 4

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 595094311-{4-[5-(2-Fluorobiphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]benzyl}piperidine-4,4-dicarboxylic acid benzyl ester

생성물 1

HCID 595094421-{4-[5-(2-Fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(morpholine-4-carbonyl)-piperidine-4-carboxylic acid benzyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

1-Hydroxybenzotriazole (0.183 g, 0.0012 mol) is added to a stirred 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) in tetrahydrofuran (20 mL). Reaction mixture is stirred for 30 minutes at room temperature. Morpholine (0.13 mL, 0.0015 mol) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (0.288 g, 0.0015 mol) are added to the reaction mixture and stirred for over night at room temperature. Demineralized water (10 mL) is added to the reaction mixture, tetrahydrofuran layer is separated and the aqueous layer is extracted with ethyl acetate (2×15 mL). Combined organic layer is dried over sodium sulphate and concentrated under reduced pressure to yield a crude viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, ethyl acetate) to get 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(morpholine-4-carbonyl)-piperidine-4-carboxylic acid benzyl ester.

후처리

  1. customReaction mixture
  2. stirringstirred for over night at room temperature
  3. customis separated
  4. extractionthe aqueous layer is extracted with ethyl acetate (2×15 mL)
  5. dry with materialCombined organic layer is dried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customto yield a crude viscous liquid, which
  8. customis purified by column chromatography (silica gel 230-400 mesh, ethyl acetate)

출처 및 근거

ORD 기록
ord-f9ea3acc79e24f94b03d5da6edb83a7d
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809539B2

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