Trifluoroacetic anhydride → 6-{4-[6-(4-Fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-pyridine-2-carboxylic acid methyl ester

HRID 2195064Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2195064
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7](O)[N:6]=1)=[O:4].FC(F)(F)C(OC(=O)C(F)(F)F)=O.[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[CH:38]=[C:37]([N:39]3[CH2:44][CH2:43][NH:42][CH2:41][C@H:40]3[CH3:45])[N:36]=[C:35]([N:46]3[CH2:50][CH2:49][CH2:48][C@H:47]3[CH3:51])[N:34]=2)=[CH:29][CH:28]=1.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl.CC(N(C)C)=O.O>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH3:11])=[C:7]([N:42]2[CH2:43][CH2:44][N:39]([C:37]3[CH:38]=[C:33]([C:30]4[CH:29]=[CH:28][C:27]([F:26])=[CH:32][CH:31]=4)[N:34]=[C:35]([N:46]4[CH2:50][CH2:49][CH2:48][C@H:47]4[CH3:51])[N:36]=3)[C@H:40]([CH3:45])[CH2:41]2)[N:6]=1)=[O:4]

Komponenten

8

Edukt 4

HCID 9845Trifluoroacetic anhydrideHCID 81531DiisopropylethylamineHCID 591683354-(4-Fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidineHCID 178497865HCID 178497865, Verbindung

Produkt 1

HCID 591683776-{4-[6-(4-Fluoro-phenyl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidin-4-yl]-3-(R)-methyl-piperazin-1-yl}-5-methyl-pyridine-2-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittel2×HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a cold solution (0° C.) of 6-hydroxy-5-methyl-pyridine-2-carboxylic acid methyl ester (Adamczyk et. al. (2002) Tetrahedron 58:6951-6963) (167 mg, 1.0 mmol) in CHCl3 (15 mL), add trifluoroacetic anhydride (423 mg, 1.5 mmol) dropwise followed by TEA (202 mg, 2.0 mmol). Stir the mixture for 1 h. Dilute with CHCl3, wash with sat. NaHCO3, dry the organic layer (Na2SO4) and concentrate under reduced pressure. Mix the residue with 4-(4-fluoro-phenyl)-6-(2-(R)-methyl-piperazin-1-yl)-2-(2-(R)-methyl-pyrrolidin-1-yl)-pyrimidine (426 mg, 1.2 mmol) and DIEA (129 mg, 1.0 mmol) in DMA. Heat the mixture at 100° C. for 16 h. Dilute with water, extract with EtOAc, and wash with brine. Dry the organic layer (Na2SO4) and concentrate under reduced pressure. Purify the residue by flash column eluting with EtOAc-Hexanes (1:5) to afford the title compound.

Aufarbeitung

  1. washwash with sat. NaHCO3
  2. dry with materialdry the organic layer (Na2SO4)
  3. concentrationconcentrate under reduced pressure
  4. extractionextract with EtOAc
  5. washwash with brine
  6. dry with materialDry the organic layer (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash column
  9. washeluting with EtOAc-Hexanes (1:5)

Quellen und Nachweise

ORD-Eintrag
ord-abc22f6caa0a477e9260c24c107161bc
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08334382B2

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