Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate → HCID 86648472、化合物

HRID 43453ノート

反応式

HRID 43453 の反応式
[CH2:1]([Li])CCC.[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=O)[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.[Cl-].[Na+].O>[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=[CH2:1])[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]

参加物

6

反応物 2

HCID 86648470Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylateHCID 178418339Butyllithium

生成物 1

HCID 86648472HCID 86648472、化合物収率 21%

試薬・触媒・溶媒 3

HCID 74505Methyltriphenyliphosphonium bromide触媒HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
-78 °C

実験手順

Methyltriphenylphosphonium bromide (0.19 g, 0.53 mmol) was suspended in THF (4 mL), followed by cooling to −78° C. An n-butyllithium/1.58 M hexane solution (0.34 mL, 0.54 mmol) was added dropwise, followed by stirring for 25 minutes. Ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained in Example (28a) (74 mg, 0.16 mmol) was added, and the mixture was heated to room temperature and stirred for one hour. Brine was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1) to obtain 15 mg of the title compound as a pale yellow solid (21%).

後処理

  1. temperaturethe mixture was heated to room temperature
  2. stirringstirred for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentration under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1)

出典と根拠

ORDレコード
ord-9aa5642329554c0bbec9a27c84c2ddbe
出典データセット
uspto-grants-2013_09
特許番号
US08536197B2

反応ノート

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