Cesium carbonate → 4-cyclopropyl-5-fluoro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

HRID 1039913Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1039913
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:8]=1)[NH2:5].Cl[C:15]1[N:20]=[C:19]([CH:21]2[CH2:23][CH2:22]2)[C:18]([F:24])=[CH:17][N:16]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:21]1([C:19]2[C:18]([F:24])=[CH:17][N:16]=[C:15]([NH:5][C:4]3[CH:6]=[C:7]([C:9]4[S:13][CH:12]=[N:11][CH:10]=4)[CH:8]=[C:2]([CH3:1])[CH:3]=3)[N:20]=2)[CH2:23][CH2:22]1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 584563653-Methyl-5-(1,3-thiazol-5-yl)anilineHCID 772310692-chloro-4-cyclopropyl-5-fluoroPyrimidine

Produkt 1

HCID 584562534-cyclopropyl-5-fluoro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amineAusbeute 91,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

3-Methyl-5-(1,3-thiazol-5-yl)aniline (0.250 g, 1.31 mmol), the product of Step 1 (0.227 g, 1.31 mmol), palladium(II) acetate (0.0295 g, 0.131 mmol), xantphos (0.114 g, 0.197 mmol), and cesium carbonate (0.856 g, 2.63 mmol) were added to a dry flask. The flask was degassed with argon and then dioxane (4.4 ml) was added. The reaction'mixture was'degassed with argon for 5 minutes, and then heated to 100° C. After 2 hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc/dichloromethane gradient) to afford 4-cyclopropyl-5-fluoro-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (0.390 g, 1.20 mmol, 91% yield). MS ESI: [M+H]+ m/z 326.8. 1H NMR (500 MHz, DMSO-d6) δ 9.59 (s, 1H); 9.06 (s, 1H); 8.38 (d, J=2.5 Hz, 1H); 8.19 (s, 1H); 7.94 (s, 1H); 7.39 (s, 1H); 7.10 (s, 1H); 2.29 (s, 3H); 2.28-2.23 (m, 1H); 1.18-1.14 (m, 4H).

Aufarbeitung

  1. customThe flask was degassed with argon
  2. additiondioxane (4.4 ml) was added
  3. waitAfter 2 hours
  4. temperaturethe reaction mixture was cooled to room temperature
  5. additiondiluted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (EtOAc/dichloromethane gradient)

Quellen und Nachweise

ORD-Eintrag
ord-35c9479745784438b0e8fd6481d22b5f
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08551984B2

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