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

HRID 2274256Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2274256
[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

Komponenten

7

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 30318Osmium TetroxideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-ce76a1e6343c47aa8f85d49db82fdcb2
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09126950B2

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