Reaktion #160879

Reaktionsgleichung

Cyclopropyl magnesium bromide

solution

N-{4-[4-amino-6-formyl-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoro-methyl)pyridin-2-yl]urea

Dess-Martin periodinane

→

above compound

Ausbeute 12.3%

N-{4-[4-amino-6-(cyclopropylcarbonyl)-7-(morpholin-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[4-(trifluoromethyl)pyridin-2-yl]urea

Ausbeute 12.3%

Lösungsmittel

THF

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas complete by HPLC (1 hour)
2. 2
   workup.ADDITIONAdditional amounts of the grinard reagent were added
3. 3
   SonstigeThe reaction was quenched with methanol
4. 4
   workup.ADDITIONby adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc
5. 5
   WaschenThe organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln
6. 6
   TrocknenThe organic layer was dried over Na2SO4
7. 7
   Einengenconcentrated
8. 8
   workup.DISSOLUTIONThe crude intermediate was dissolved in DMSO (3 nth)
9. 9
   workup.STIRRINGto stir until the reaction
10. 10
    Sonstigewas complete by HPLC (2 hours)
11. 11
    Waschenwashed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution
12. 12
    TrocknenThe organic layer was dried over Na2SO4
13. 13
    Einengenconcentrated
14. 14
    Sonstigeto give a crude solid which
15. 15
    Sonstigewas purified by HPLC (10-70% ACN/H2O)

Vorschrift

Cyclopropyl magnesium bromide (7.40 mL, 3.70 mmol, 0.5 M in diethyl ether) was added dropwise to a stirring solution of Example 85 (200 mg, 0.37 mmol) in THF (10 mL). This was allowed to stir until the reaction was complete by HPLC (1 hour). Additional amounts of the grinard reagent were added as needed. The reaction was quenched with methanol and was worked up by adding 1 volume of saturated NH4Cl solution and 5 volumes of EtOAc. The organic layer was washed 2× with NH4Cl and 1× with sodium carbonate soln. The organic layer was dried over Na2SO4 and concentrated. The crude intermediate was dissolved in DMSO (3 nth) and treated with Dess-Martin periodinane (174.7 mg, 0.412 mmol). The reaction was allowed to stir until the reaction was complete by HPLC (2 hours). The reaction was diluted with EtOAc (200 mL) and washed 2× with both saturated NaHCO3 and 2M sodium thiosulfate solution. The organic layer was dried over Na2SO4 and concentrated to give a crude solid which was purified by HPLC (10-70% ACN/H2O) to give 26.3 mg of the above compound (0.04 mmol, 12.3% yield). 1H-NMR (DMSO-d6). δ 9.98 (s, 1H), 9.82 (s, 1H), 8.60 (d, J=5.4 Hz, 1H), 8.11 (s, 1H), 8.03 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.45-7.41 (m, 3H), 4.08 (s, 2H), 3.55-3.52 (m, 4H), 2.46-2.43 (m, 4 H), 2.07-1.97 (m, 1H), 0.95-0.91 (m, 2H), 0.74-0.69 (m, 2H). MS [M+H]+=581; LCMS RT=2.68 min.

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