2,4-Dichloro-5-fluoropyrimidine → 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine

HRID 1725695

Reaktionsgleichung

Reaktionsgleichung von HRID 1725695
[CH2:1]([O:4][C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)[C:2]#[CH:3].[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([F:20])=[CH:15][N:14]=1>CO.O.CCOC(C)=O>[Cl:12][C:13]1[N:18]=[C:17]([NH:9][C:8]2[CH:10]=[CH:11][C:5]([O:4][CH2:1][C:2]#[CH:3])=[CH:6][CH:7]=2)[C:16]([F:20])=[CH:15][N:14]=1

Komponenten

5

Edukt 2

HCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 126688624-(Prop-2-yn-1-yloxy)aniline

Produkt 1

HCID 575628992-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamineAusbeute 243,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 22242641Methanol--water (1/1)Lösungsmittel

Versuchsvorschrift

Crude 4-(prop-2-ynyloxy)aniline (0.750 g, 5.10 mmol) and 2,4-dichloro-5-fluoropyrimidine (1.27 g, 0.760 mmol) were stirred in MeOH/water (4:1, 35 mL) at room temperature for 18 h. The reaction mixture was diluted with EtOAc (200 mL) and washed with 1N HCl (50 mL) and brine (50 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10)) to provide 2-chloro-5-fluoro-N4-[4-(prop-2-ynyloxy)phenyl]-4-pyrimidineamine as a light brown solid (0.514 g). 1H NMR (CDCl3): δ 8.03 (d, J=2.7 Hz, 1H), 7.53 (d, J=8.7 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 6.86 (s, 1H), 4.71 (d, J=2.4 Hz, 2H), 2.55 (t, J=2.4 Hz, 1H); LCMS: purity: 99%; MS (m/e): 279 (MH+).

Aufarbeitung

  1. washwashed with 1N HCl (50 mL) and brine (50 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (silica gel, hexanes ramped to EtOAc:hexanes (1:10))

Quellen und Nachweise

ORD-Eintrag
ord-e54284acc95f4d05997c14a84c603153
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07491732B2

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