반응 #595330

반응 방정식

cyclopropanesulfonyl chloride

cyclopropanesulfonyl chloride

NaH

NaOH

HCl

NaH

1-(2-fluoro-4-iodophenyl)-5,7-dimethyl-1H-imidazo[4,5-c]pyridine-2,6(3H,5H)-dione

→

N-(4-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)cyclopropanesulfonamide

수율 35.0%

용매

THF

DMF

반응 조건

후처리

1. 1
   온도cooled to below 0° C. under an ice-bath
2. 2
   기타The cooling bath was removed
3. 3
   workup.ADDITIONafter addition
4. 4
   온도The same solution was re-cooled to −5° C. in a dry-ice/acetone bath
5. 5
   온도to warm to room temperature
6. 6
   workup.STIRRINGstirred
7. 7
   workup.WAITwas and additional 16 hours
8. 8
   온도The reaction mixture was cooled to 0° C.
9. 9
   workup.ADDITIONwere added
10. 10
    workup.STIRRINGThe solution was stirred at room temperature for additional 5 hours
11. 11
    온도The mixture was heated to 65° C. for 40 minutes
12. 12
    온도After cooled to room temperature
13. 13
    추출was extracted with EtOAc (15 mL×3)
14. 14
    세척The combined organic layers was washed with brine
15. 15
    건조dried (MgSO4)
16. 16
    농축concentrated under the reduced pressure
17. 17
    기타to give a residue, which
18. 18
    기타purified

실험 절차

To the solution of 1-(2-fluoro-4-iodophenyl)-5,7-dimethyl-1H-imidazo[4,5-c]pyridine-2,6(3H,5H)-dione (23 mg, 0.0576) dissolved in dry DMF (2 mL) cooled to below 0° C. under an ice-bath, was added NaH (60% in mineral oil) (5.0 mg, 0.125 mmol). The cooling bath was removed after addition and the solution was allowed to stir at room temperature for 1 hour. The same solution was re-cooled to −5° C. in a dry-ice/acetone bath, and added cyclopropanesulfonyl chloride (28 mg, 0.20 mmol) dissolved in dry THF (0.5 mL) slowly. The mixture was allowed to warm to room temperature and stirred was and additional 16 hours. The reaction mixture was cooled to 0° C., additional NaH (60% in oil) (5.0 mg, 0.125 mmol), followed by cyclopropanesulfonyl chloride (15 mg, 0.11 mmol) were added. The solution was stirred at room temperature for additional 5 hours. To the same reaction mixture was added aqueous NaOH (1N) (5 mL). The mixture was heated to 65° C. for 40 minutes. After cooled to room temperature, aqueous HCl (1N) (25 mL) was added to acidify the solution, which was extracted with EtOAc (15 mL×3). The combined organic layers was washed with brine, dried (MgSO4), and concentrated under the reduced pressure to give a residue, which was HPLC purified. (9.6 mg, 35% yield). MW m/z: 478.08 (MW+1), 476.10 (MW−1). 1H NMR (DMSO-d6, 300 Hz): δ ppm 8.89 (s, 7.65 (s, 1H), 7.56 (dd, J=10.8, 1.5 Hz, 1H), 7.42 (s, 1H), 7.0 (d, J=8.7 Hz, 1H), 6.34 (t, J=8.7 Hz, 1H), 3.43 (s, 3H), 2.43 (m, 2H), 1.65 (s, 3H), 0.69-0.79 (m, 4H)

출처