Water → N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

HRID 2274256ノート

反応式

HRID 2274256 の反応式
[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23](NC(=O)C=C)C=C[CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.C[N+:33]1([O-])[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1.[C:40](OCC)(=[O:42])C.[OH2:46]>C1COCC1.O=[Os](=O)(=O)=O>[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:26]=[C:38]([NH:33][C:34](=[O:46])[CH:35]([OH:36])[CH2:40][OH:42])[CH:37]=[CH:23][CH:22]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:13][CH:14]=2)=[N:6][CH:7]=1

参加物

7

反応物 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 59174488Spebrutinib

生成物 1

HCID 72165218N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide

試薬・触媒・溶媒 2

HCID 30318Osmium Tetroxide触媒HCID 8028Tetrahydrofuran溶媒

実験手順

In a 25 mL 3-neck RBF equipped with a calcium chloride guard tube N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)acrylamide (0.275 g) in THF (8 mL), NMO (0.07 g) and OsO4 (4% in water) solution were charged at room temperature. The reaction mixture was stirred at room temperature for 3 to 4 h. The reaction was monitored on TLC using ethyl acetate (100%) as mobile phase. After completion, the reaction mixture was poured into water and extracted into ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and concentrated under reduced pressure at 40° C. Crude material was purified by Combiflash chromatography. Product was eluted with 90% ethyl acetate in hexane to give 0.08 g of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-2,3-dihydroxypropanamide. M+H=457.8 1H NMR: DMSO-d6 (400 MHz): 3.28 (s, 3H), 3.60 (m, 4H), 4.04 (m, 3H), 4.82 (t, 1H, J=5.6), 5.78 (d, 1H, J=5.6), 6.79 (d, 2H, J=8.8), 7.26 (d, 1H, J=8), 7.43 (d, 1H, J=8), 7.52 (d, 3H, J=9.2), 7.97 (s, 1H), 8.05 (d, 1H, J=3.6), 8.98 (s, 1H), 9.34 (s, 1H), 9.55 (s, 1H).

後処理

  1. additionwere charged at room temperature
  2. extractionextracted into ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure at 40° C
  6. customCrude material was purified by Combiflash chromatography
  7. washProduct was eluted with 90% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-ce76a1e6343c47aa8f85d49db82fdcb2
出典データセット
uspto-grants-2015_09
特許番号
US09126950B2

反応ノート

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