Bromide ion → HCID 46893386, Verbindung

HRID 625808

Reaktionsgleichung

Reaktionsgleichung von HRID 625808
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]([O:14]CC)=O)[N:3]=1.[Br-].Cl.[Na+].[Cl-].[CH3:21][C:22]1[NH:26][N:25]=[C:24]([NH2:27])[CH:23]=1.[I-].[K+].CCN(C(C)C)[CH:33]([CH3:35])[CH3:34].[CH2:39]1[CH2:43][O:42][CH2:41][CH2:40]1>CN(C=O)C.O>[CH3:41][O:42][C:43]1[CH:39]=[CH:40][CH:35]=[CH:33][C:34]=1[C:12]([C:4]1[N:3]=[C:2]([NH:27][C:24]2[CH:23]=[C:22]([CH3:21])[NH:26][N:25]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1)=[O:14]

Komponenten

11

Edukt 8

HCID 259Bromide ionHCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 5234Sodium ChlorideHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 3477840Ethyl 4-chloroquinazoline-2-carboxylate

Produkt 1

HCID 46893386HCID 46893386, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
-40 °C

Versuchsvorschrift

To a solution of ethyl 4-chloroquinazoline-2-carboxylate (500 mg, 2.11 mmol) in THF (20 mL) at −40° C. was added dropwise 1M 2-methoxyphenylmagnesum bromide (2.6 mL, 2.5 mmol) and the mixture was stirred at −40° C. for 4 h. To the mixture were added 1N HCl to pH<2 and saturated aq NaCl (50 mL), and the mixture was extracted with EtOAc (3×80 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. To the residue (673 mg) were added a solution of 5-methyl-1H-pyrazol-3-amine (247 mg, 2.84 mmol) in DMF (8 mL), potassium iodide (387 mg, 2.33 mmol), and DIEA (822 mg, 6.36 mmol), and the mixture was stirred at rt overnight and then at 50° C. for 5 h and then at 80° C. for 2 h. The mixture was allowed to cool to rt and then H2O (30 mL) was added. The mixture was stirred and cooled to 0° C., and the precipitated solid was collected by filtration and washed with MeOH. A portion of the solid was purified by preparative reverse phase HPLC to afford (2-methoxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone. 1H NMR (300 MHz, DMSO-d6) δ 2.11 (s, 3H), 3.48 (s, 3H), 6.15 (s, 1H), 7.11-7.18 (m, 2H), 7.56-7.64 (m, 3H), 7.56 (bs, 2H), 8.70 (d, 1H), 10.58 (s, 1H), 12.11 (s, 1H); LC-MS (ESI) m/z 360 (M+H)+.

Aufarbeitung

  1. extractionthe mixture was extracted with EtOAc (3×80 mL)
  2. washThe combined organic layers were washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. stirringthe mixture was stirred at rt overnight
  7. waitat 50° C. for 5 h
  8. waitat 80° C. for 2 h
  9. temperatureto cool to rt
  10. stirringThe mixture was stirred
  11. temperaturecooled to 0° C.
  12. filtrationthe precipitated solid was collected by filtration
  13. washwashed with MeOH
  14. customA portion of the solid was purified by preparative reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9b26f1c6df9846479cebee76f2577a07
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09308207B2

Verknüpfte Notizen

Wird geladen…