1-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidine → 4-[2-(5-Benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

HRID 645521노트

반응식

HRID 645521 반응식
[CH2:1]([NH:8][C:9]([C:11]1[C:12]([Cl:20])=[N:13][C:14]([S:18][CH3:19])=[N:15][C:16]=1Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][OH:42])[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>C1COCC1>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH:37]([CH2:40][CH2:41][O:42][C:16]2[C:11]([C:9](=[O:10])[NH:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[C:12]([Cl:20])[N:13]=[C:14]([S:18][CH3:19])[N:15]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]

참가 물질

5

반응물 3

HCID 8541401-(tert-Butoxycarbonyl)-4-(2-hydroxyethyl)piperidineHCID 23665647Potassium tert-butoxideHCID 86627801N-benzyl-4,6-dichloro-2-(methylthio)pyrimidine-5-carboxamide

생성물 1

HCID 866278024-[2-(5-Benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

To a solution of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carboxylic acid benzylamide (3 mmol) in THF (20 mL) is added KOtBu (3.6 mmol) at 0° C. under N2. After stirred at 0° C. for 20 min, the above mixture is added dropwise to a solution of 4-(2-hydroxyethyl)piperidine-1-carboxylic acid tert-butyl ester (3.3 mmol) in THF (20 mL) at −78° C. The resulting mixture is gradually warm up to −30° C. over 2.5 h. The reaction is quenched by the addition of H2O. The mixture is extracted twice with AcOEt. The organic layer is dried over Na2SO4, filtered, and concentrated to give 4-[2-(5-benzylcarbamoyl-6-chloro-2-methylsulfanylpyrimidin-4-yloxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester as a white solid; 1H-NMR (CDCl3), δ 1.07-1.17 (2H, m), 1.48 (9H, s), 1.62-1.70 (2H, m), 2.54 (3H, s), 2.64 (2H, br t), 4.06 (2H, m), 4.45 (2H, t), 4.64 (2H, d), 6.06 (1H, t), 7.30-7.34 (2H, m), 7.35-7.36 (3H, m).

후처리

  1. temperatureThe resulting mixture is gradually warm up to −30° C. over 2.5 h
  2. customThe reaction is quenched by the addition of H2O
  3. extractionThe mixture is extracted twice with AcOEt
  4. dry with materialThe organic layer is dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bcee3dc6e04a4117a90ecb420e86a0ef
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07704996B2

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