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Sodium hydride → 4-[5-Acetyl-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1174743
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HRID 1174743 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]2[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:32][CH:33]=2)[N:21]=[CH:20][N:19]=1>CN(C)C(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]3[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:32][CH:33]=3)[N:21]=[CH:20][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
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참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 865973601-[4-Chloro-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone

생성물 1

HCID 112488854-[5-Acetyl-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Tert-Butyl Ester수율 50.4%

시약·촉매·용매 1

HCID 31374
Dimethylacetamide
용매

실험 절차

4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (3.2 mmol, 633 mg) and sodium hydride (3.2 mmol, 76 mg) were dissolved in N,N-dimethyl acetamide (1.5 mL) and stirred for 30 minutes at room temperature. Subsequently, compound 1-[4-chloro-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone (0.63 mmol, 207 mg) was added. The reaction was stirred at 70° C. for 30 minutes. Progress of the reaction was monitored by thin layer chromatography and LCMS. Sodium hydride was carefully quenched with water and the desired compound was extracted with ethyl acetate. Organic solvents were evaporated in vacuo and purified by flash chromatography (Silica gel 60; 50/50 EtOAc/Hexanes) to afford Compound A37 as a yellow solid (156 mg, 50%). 1H NMR (400 MHz, CDCl3) δ (ppm): 12.19 (s, 1H), .95 (s, 1H), 8.56 (d, 1H), 8.44 (s, 1H), 8.07 (d, 1H), 5.56 (h, 1H), 3.82 (m, 2H), 3.31 (m, 2H), 3.23 (s, 3H), 2.70 (s, 3H), 2.11 (m, 2H), 1.85 (m, 2H), 1.48 (s, 9H). LCMS (ESI), m/z 492.4 (M+H+, 100%).

후처리

  1. stirringThe reaction was stirred at 70° C. for 30 minutes
  2. customSodium hydride was carefully quenched with water
  3. extractionthe desired compound was extracted with ethyl acetate
  4. customOrganic solvents were evaporated in vacuo
  5. custompurified by flash chromatography (Silica gel 60; 50/50 EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-b50e6348a491457fad3d1cea8716e7e9
출처 데이터셋
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07838525B2

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