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, 화합물

HRID 1424922노트

반응식

HRID 1424922 반응식
[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]

참가 물질

6

반응물 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

생성물 1

HCID 86648472HCID 86648472, 화합물수율 21%

시약·촉매·용매 3

HCID 74505Methyltriphenyliphosphonium bromide촉매HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
-78 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-72393f5567944fdba13c67b1a1b13115
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927588B2

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