Bromine → N-[3-(2-bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410379Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 410379
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:11]=[C:12]([NH:21][C:22]2[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=2)[CH:13]=[C:14]([C:16]2[S:20][CH:19]=[N:18][CH:17]=2)[CH:15]=1.[Br:32]Br>C1COCC1>[Br:32][C:19]1[S:20][C:16]([C:14]2[CH:13]=[C:12]([NH:21][C:22]3[N:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=[CH:24][N:23]=3)[CH:11]=[C:10]([CH3:9])[CH:15]=2)=[CH:17][N:18]=1

Komponenten

5

Edukt 3

HCID 24408BromineHCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Produkt 1

HCID 58456233N-[3-(2-bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amineAusbeute 66,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Lithium diisopropylamide (1.8 M in THF/heptane/ethylbenzene, 11.4 mL, 20.5 mmol) was cooled to −70° C. Intermediate 4 (2.3 g, 6.8 mmol) in THF (23 mL) was added slowly over 15 minutes, keeping the temperature at −65° C. The reaction was allowed to stir for 30 minutes following the addition and then bromine (0.53 mL, 10.3 mmol) was added. The reaction was stirred for 30 minutes and then quenched with 20 mL of water and warmed to rt. The reaction was diluted with EtOAc (50 mL). The layers were separated and the organic portion was washed with Na2SO3 (10% aqueous), brine, dried over MgSO4 and concentrated in vacuo. Purification via column chromatography (ISCO, dry load with silica gel, Hexane-50% EtOAc:Hexane) to provide N-[3-(2-bromo-1,3-thiazol-5-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine (1.88 g, 4.53 mmol, 66%). MS APCI: [M+H]+ m/z 414.8, 416.8. 1H NMR (600 MHz, CDCl3) δ 8.64 (d, J=4.9, 1H), 7.88 (s, 1H), 7.74 (s, 1H), 7.33 (s, 1H), 7.05 (t, J=6.4, 1H), 7.01 (s, 1H), 2.38 (s, 3H).

Aufarbeitung

  1. customat −65° C
  2. additionthe addition
  3. stirringThe reaction was stirred for 30 minutes
  4. customquenched with 20 mL of water
  5. additionThe reaction was diluted with EtOAc (50 mL)
  6. customThe layers were separated
  7. washthe organic portion was washed with Na2SO3 (10% aqueous), brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification
  11. dry with materialvia column chromatography (ISCO, dry load with silica gel, Hexane-50% EtOAc:Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-7f3d9e73d96d432796b67edd67cc6e4f
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08759366B2

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