Morpholine → tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 1184162ノート

反応式

HRID 1184162 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([C:19]([C:21]2[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:24]3[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=3[N:22]=2)=[O:20])[CH2:15][CH:16]([CH3:18])[CH3:17])[CH2:11][C@@H:10]([C:36](O)=[O:37])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:39]1[CH2:44][CH2:43][O:42][CH2:41][CH2:40]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:31][O:30][CH2:29][CH2:28][CH2:27][CH2:26][N:25]1[C:24]2[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=2[N:22]=[C:21]1[C:19]([N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C@H:12]1[CH2:11][C@@H:10]([C:36]([N:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[O:37])[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13]1)=[O:20]

参加物

7

反応物 5

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 58355779(3R,5S)-(tert-butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid

生成物 1

HCID 58355127tert-butyl (3S,5R)-3-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate収率 80.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

(3R, 5S)-1-(tert-Butoxycarbonyl)-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-3-carboxylic acid (10 g) and morpholine (1.6 g) were dissolved in DMF (100 ml), WSC.HCL (4.8 g) and HOBt (3.1 g) were added, and the mixture was stirred at 50° C. for 12 hr. The reaction mixture was poured into 10% aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extracts were combined, washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:1-1:0) was concentrated under reduced pressure to give the object product (8.9 g).

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (1:1-1:0)
  6. concentrationwas concentrated under reduced pressure

出典と根拠

ORDレコード
ord-ffbe80ed4edb4699a7f8032250a79b4d
出典データセット
uspto-grants-2014_03
特許番号
US08664380B2

反応ノート

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