Hydrochloric Acid → N-{3-Bromo-5-[(methylsulfanyl)methyl]phenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amine

HRID 2277755Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2277755
Cl.O1CCOCC1.Cl[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[O:22][CH3:23])[C:12]([F:24])=[CH:11][N:10]=1.[Br:25][C:26]1[CH:27]=[C:28]([CH:30]=[C:31]([CH2:33][S:34][CH3:35])[CH:32]=1)[NH2:29]>C(O)CCC.C(OCC)(=O)C>[Br:25][C:26]1[CH:27]=[C:28]([NH:29][C:9]2[N:14]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[O:22][CH3:23])[C:12]([F:24])=[CH:11][N:10]=2)[CH:30]=[C:31]([CH2:33][S:34][CH3:35])[CH:32]=1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 867296092-Chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidineHCID 894447523-Bromo-5-[(methylsulfanyl)methyl]aniline

Produkt 1

HCID 89444631N-{3-Bromo-5-[(methylsulfanyl)methyl]phenyl}-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidin-2-amineAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2631-ButanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

A 4N solution of hydrogen chloride in dioxane (0.54 mL; 2.15 mmol) was added to a stirred solution of 2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (553 mg; 2.15 mmol) and 3-bromo-5-[(methylsulfanyl)methyl]aniline (500 mg; 2.15 mmol) in 1-butanol (4.8 mL). The batch was stirred at 140° C. for 8 hours. After cooling the batch was diluted with ethyl acetate and washed with sodium bicarbonate and saturated aqueous sodium chloride solution. The organic phase was filtered using a Whatman filter and concentrated. The residue was purified by chromatography (hexane/ethyl acetate 4:1) to give the desired product (450 mg; 0.99 mmol).

Aufarbeitung

  1. temperatureAfter cooling the batch
  2. washwashed with sodium bicarbonate and saturated aqueous sodium chloride solution
  3. filtrationThe organic phase was filtered
  4. filtrationfilter
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (hexane/ethyl acetate 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-3d69db03f8594a7e898c8ea8dfda43ef
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133171B2

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