Reaktion #160882

Reaktionsgleichung

ether

thionyl chloride

L-Selectride

N-{4-[4-amino-6-(hydroxymethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea

→

title compound

Ausbeute 84.0%

N-[4-(4-amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)phenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Ausbeute 84.0%

Lösungsmittel

—

hexanes

THF

THF

THF

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenAfter 30 min the reaction was concentrated under vacuum
2. 2
   Sonstigesonicated briefly
3. 3
   Einengenconcentrated again under vacuum (2×)
4. 4
   workup.WAITAfter 15 min the reaction was complete by HPLC
5. 5
   SonstigeThe reaction mixture was removed from the ice bath
6. 6
   Sonstigequenched with MeOH (1 mL)
7. 7
   workup.ADDITIONtreated with 1 M sodium hydroxide (2 mL) and 30% hydrogen peroxide (2 mL)
8. 8
   workup.ADDITIONthe mixture was diluted with EtOAc (200 mL) and water (200 mL)
9. 9
   WaschenThe organic layer was washed with brine
10. 10
    Trocknendried with sodium sulfate

Vorschrift

A suspension of N-{4-[4-amino-6-(hydroxymethyl)pyrrolo[2,1-f][1,2,4]-triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea (423 mg, 0.930 mmol) in THF 5 (mL) and 1,2-dichloroethane (5 mL) was treated with thionyl chloride (148 uL, 2.05 mmol) at rt. After 10 min the reaction appeared complete by RP-HPLC. After 30 min the reaction was concentrated under vacuum. The residue was suspended in 1,2-dichloroethane and sonicated briefly, then concentrated again under vacuum (2×). The resulting solid (412 mg, 0.86 mmol) was suspended in THF (20 mL) and cooled to −45° C. This suspension was treated with 1.0 M L-Selectride in THF (8.6 mL, 8.6 mmol). After 15 min the reaction was complete by HPLC. The reaction mixture was removed from the ice bath and quenched with MeOH (1 mL), then treated with 1 M sodium hydroxide (2 mL) and 30% hydrogen peroxide (2 mL). After 15 min stirring, the mixture was diluted with EtOAc (200 mL) and water (200 mL). The organic layer was washed with brine and dried with sodium sulfate. Concentration of the organic layer and trituration with ether:hexanes gave the title compound as an white powder (323 mg, 0.73 mmol, 84% yield). 1H-NMR (CD3OD-d6) δ 8.61 (d, J=8 Hz, 1H), 7.73 (s, 1H), 7.62 (d, J=9 Hz, 2H), 7.48 to 7.50 (m, 1H), 7.35 (d, J=9 Hz, 2H), 7.31 to 7.36 (m, 2H), 2.14 (s, 3H); MS [M+H]+=445.1; LCMS RT=2.80.

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