Nitrogen → 3-((3-((5-Fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate

HRID 2274257노트

반응식

HRID 2274257 반응식
N#N.[F:3][C:4]1[C:5]([NH:22][C:23]2[CH:24]=[C:25]([NH:29][C:30](=[O:35])[CH:31]([OH:34])[CH2:32][OH:33])[CH:26]=[CH:27][CH:28]=2)=[N:6][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:13][CH:12]=2)=[N:8][CH:9]=1.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C1COCC1.C(OCC)(=O)C>[CH3:36][S:37]([O:33][CH2:32][CH:31]([OH:34])[C:30]([NH:29][C:25]1[CH:26]=[CH:27][CH:28]=[C:23]([NH:22][C:5]2[C:4]([F:3])=[CH:9][N:8]=[C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][CH3:21])=[CH:13][CH:12]=3)[N:6]=2)[CH:24]=1)=[O:35])(=[O:39])=[O:38]

참가 물질

6

반응물 3

HCID 947NitrogenHCID 31297Methanesulfonyl chlorideHCID 72165218N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

생성물 1

HCID 902338843-((3-((5-Fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate수율 32%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매2회

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온도
0 °C

실험 절차

In a 25 mL 3-neck RBF equipped with N2-bubbler and thermo-pocket, N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide (I-4) (0.08 g) was dissolved in THF (5 mL), TEA (0.0212 g) was added at room temperature. The reaction mixture was cooled to 0° C. Methane sulphonyl chloride (0.021 g) was slowly added at 0° C. The reaction mixture was stirred at room temperature for 1 h. The reaction was monitored on TLC by using ethyl acetate (100%) as mobile phase. (Only 50% of the reaction was complete on TLC). The reaction was diluted with ethyl acetate (20 mL), washed with saturated NaHCO3 (25 mL). The organic layer was separated and dried over sodium sulfate. Ethyl acetate was removed under reduced pressure at 40° C. Crude material was purified by Combiflash chromatography eluted with 7% ethyl acetate in hexane. The solvent was removed under vacuum to give 0.03 g of 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate.

후처리

  1. washwashed with saturated NaHCO3 (25 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. customEthyl acetate was removed under reduced pressure at 40° C
  5. customCrude material was purified by Combiflash chromatography
  6. washeluted with 7% ethyl acetate in hexane
  7. customThe solvent was removed under vacuum

출처 및 근거

ORD 기록
ord-87c4cc0ae4ff45259d51c4fba90c9186
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09126950B2

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