Dimethylformamide → (S)-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)-6-[2-(triisopropylsilyl)oxazol-5-yl]pyrimidine-2,4-diamine

HRID 1187686Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1187686
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH3:10])[N:5]=[C:4]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:30]1[O:34][C:33]([Si:35]([CH:42]([CH3:44])[CH3:43])([CH:39]([CH3:41])[CH3:40])[CH:36]([CH3:38])[CH3:37])=[N:32][CH:31]=1)CCC.CN(C)C=O>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C@@H:9]([NH:8][C:6]2[N:5]=[C:4]([NH:18][C:19]3[CH:24]=[N:23][CH:22]=[CH:21][N:20]=3)[CH:3]=[C:2]([C:30]3[O:34][C:33]([Si:35]([CH:39]([CH3:41])[CH3:40])([CH:42]([CH3:44])[CH3:43])[CH:36]([CH3:37])[CH3:38])=[N:32][CH:31]=3)[N:7]=2)[CH3:10])=[CH:12][CH:13]=1

Komponenten

6

Edukt 3

HCID 6228DimethylformamideHCID 114971955-(Tributylstannyl)-2-(triisopropylsilyl)-1,3-oxazole2×HCID 86659380(S)-6-Chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine

Produkt 1

HCID 86659385(S)-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)-6-[2-(triisopropylsilyl)oxazol-5-yl]pyrimidine-2,4-diamineAusbeute 65,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

150 mg of (S)-6-chloro-N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)pyrimidine-2,4-diamine (Example 9), 246 mg of 5-(tributylstannyl)-2-(triisopropylsilyl)oxazole (synthesized according to the method described in WO2007/17096), and 25 mg of tetrakis(triphenylphosphine)palladium were added in turn to 5 ml of degassed dimethylformamide, and then the mixture was stirred at 100° C. for 2.5 hours under argon atmosphere. 246 mg of 5-(tributylstannyl)-2-(triisopropylsilyl)oxazole was added thereto, and the mixture was further stirred for four hours. The reaction solution was diluted with water, and then subjected to extraction with ethyl acetate. The organic layer was washed in turn with water and brine, and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 153 mg of (S)—N2-[1-(4-fluorophenyl)ethyl]-N4-(pyrazin-2-yl)-6-[2-(triisopropylsilyl)oxazol-5-yl]pyrimidine-2,4-diamine as pale orange oil.

Aufarbeitung

  1. stirringthe mixture was further stirred for four hours
  2. extractionsubjected to extraction with ethyl acetate
  3. washThe organic layer was washed in turn with water and brine
  4. dry with materialdried over magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-6cee3c54d1664183b635ab14e9f0d93a
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08673891B2

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