Water → 2-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethylsulfanyl}-propionic acid ammonium salt

HRID 1288885Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1288885
Cl.Cl[CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[CH:24])[CH:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH2:26][CH2:27][O:28][CH3:29].[C:30](O)(=[S:34])[CH:31](C)O.[OH-:36].[K+].O.CN([CH:42]=[O:43])C>C(O)(=O)C>[NH4+:11].[C:23]([C:19]1[CH:18]=[C:17]([NH:16][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][S:34][CH:30]([CH3:31])[C:42]([O-:43])=[O:36])=[C:7]([O:25][CH2:26][CH2:27][O:28][CH3:29])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:22]=[CH:21][CH:20]=1)#[CH:24]

Komponenten

7

Edukt 5

HCID 962WaterHCID 6228DimethylformamideHCID 14797Potassium HydroxideHCID 18925049[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine HydrochlorideHCID 178473673HCID 178473673, Verbindung

Produkt 1

HCID 1317206302-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethylsulfanyl}-propionic acid ammonium saltAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

The title product of Example 34 (150 mg, 0.34 mmol) was added to a solution of thiolactic acid (100 μL, 1.14 mmol) and KOH (150 mg, 2.7 mmol) in degassed DMF (5 mL)/H2O (0.5 mL). The reaction mixture was stirred at 50° C. under an atmosphere of N2 for 72 hours and then cooled to room temperature. The pH of the mixture was adjusted to about 4.0 with acetic acid and then partitioned between CHCl3 and brine. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by preparative RP18 HPLC utilizing a gradient of 15% to 100% CH3CN/pH 4.5, 50 mM ammonium acetate followed by lyophilization of the appropriate pure fractions to afford the title product (28 mg; 18%; M.P. 95°-103° C. (dec); LC-MS: 468 (MH+); anal. RP-HPLC RT: 3.57 min).

Aufarbeitung

  1. temperaturecooled to room temperature
  2. custompartitioned between CHCl3 and brine
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative RP18 HPLC

Quellen und Nachweise

ORD-Eintrag
ord-498350bde5ed4f2987a3daccd99a7b73
Quelldatensatz
uspto-grants-1998_05
Patentnummer
US05747498

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