반응 #160879

반응 방정식

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

수율 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

수율 12.3%

용매

THF

EtOAc

반응 조건

후처리

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

실험 절차

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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