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 2407511ノート

反応式

HRID 2407511 の反応式
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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-f9ea3acc79e24f94b03d5da6edb83a7d
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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