Dichloromethane → 4,6-Dichloro-2-(pyrazin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidine

HRID 1295679

Reaktionsgleichung

Reaktionsgleichung von HRID 1295679
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[N:12]=C(O)[C:10]([C:14]2[C:19]([F:20])=[CH:18][C:17]([F:21])=[CH:16][C:15]=2[F:22])=[C:9](O)[N:8]=1.P(Cl)(Cl)([Cl:26])=O.C(N(CC)C(C)C)(C)C.Cl[CH2:39][Cl:40]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[Cl:26][C:9]1[C:10]([C:14]2[C:19]([F:20])=[CH:18][C:17]([F:21])=[CH:16][C:15]=2[F:22])=[C:39]([Cl:40])[N:12]=[C:7]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[N:8]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 24813Phosphorus oxychloride2×HCID 81531DiisopropylethylamineHCID 178517557HCID 178517557, Verbindung

Produkt 1

HCID 589101014,6-Dichloro-2-(pyrazin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

According to scheme 1, step c, to a mixture of 2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine-4,6-diol 4 in an aprotic solvent preferably toluene (g/ml) preferably 5–15 parts, more preferably in 5–10 parts, most preferable in 7 parts, is slowly added at about 10–15° C., phosphorus oxychloride. Following complete addition of the phosphorus oxychloride, N,N-diisopropylethyl amine in a molar ratio of about 1:1 to 1:5, preferably in the range of 1:4 is slowly added at about 10–15° C. and the mixture heated to reflux for about 6 to 24 h, preferably about 6 h. The volatiles are removed by distillation to a residue which is further distilled with toluene preferably two times to afford a further residue. The further residue is dissolved in a solvent selected from ethyl acetate, dichloromethane and toluene, preferably ethyl acetate then partitioned by pouring into water while maintaining the temperature between about 5–15° C. The solvent layer is separated, washed with water, dried over sodium sulfate and filtered through a pad of filter aid such as diatomaceous earth or through hydrous magnesium silicate and most of the volatiles removed to a residue to which is added heptane forming a precipitated product. The precipitated product 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine 5 is collected and having a purity of >95% as shown by high pressure liquid chromatography (HPLC). Further, the 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine 5 is formed and isolated without chromatography.

Aufarbeitung

  1. additionis slowly added at about 10–15° C.
  2. additionpreferably in the range of 1:4 is slowly added at about 10–15° C.
  3. temperaturethe mixture heated
  4. temperatureto reflux for about 6 to 24 h, preferably about 6 h
  5. customThe volatiles are removed by distillation to a residue which
  6. distillationis further distilled with toluene preferably two times
  7. customto afford a further residue
  8. dissolutionThe further residue is dissolved in a solvent
  9. customthen partitioned
  10. additionby pouring into water
  11. temperaturewhile maintaining the temperature between about 5–15° C
  12. customThe solvent layer is separated
  13. washwashed with water
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered through a pad of filter aid such as diatomaceous earth or through hydrous magnesium silicate and most of the volatiles
  16. customremoved to a residue to which
  17. additionis added heptane forming a precipitated product
  18. customThe precipitated product 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine 5 is collected

Quellen und Nachweise

ORD-Eintrag
ord-4b6c2e5dd2f74fdd8e18c1311d6081bb
Quelldatensatz
uspto-grants-2007_07
Patentnummer
US07244736B2

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