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

HRID 508148ノート

反応式

HRID 508148 の反応式
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17]2[C:12](=[CH:13][N:14]([CH3:20])[C:15](=[O:19])[C:16]=2[CH3:18])[NH:11]C1=O.[H-].[Na+].[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1.[OH-].[Na+].Cl>CN(C=O)C.C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:17]1[C:12]([NH:11][S:27]([CH:24]2[CH2:26][CH2:25]2)(=[O:29])=[O:28])=[CH:13][N:14]([CH3:20])[C:15](=[O:19])[C:16]=1[CH3:18]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydride2 回HCID 2760919Cyclopropanesulfonyl chloride2 回HCID 582598911-(2-fluoro-4-iodophenyl)-5,7-dimethyl-1H-imidazo[4,5-c]pyridine-2,6(3H,5H)-dione

生成物 1

HCID 24759452N-(4-(2-fluoro-4-iodophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)cyclopropanesulfonamide収率 35%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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)

後処理

  1. temperaturecooled to below 0° C. under an ice-bath
  2. customThe cooling bath was removed
  3. additionafter addition
  4. temperatureThe same solution was re-cooled to −5° C. in a dry-ice/acetone bath
  5. temperatureto warm to room temperature
  6. stirringstirred
  7. waitwas and additional 16 hours
  8. temperatureThe reaction mixture was cooled to 0° C.
  9. additionwere added
  10. stirringThe solution was stirred at room temperature for additional 5 hours
  11. temperatureThe mixture was heated to 65° C. for 40 minutes
  12. temperatureAfter cooled to room temperature
  13. extractionwas extracted with EtOAc (15 mL×3)
  14. washThe combined organic layers was washed with brine
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated under the reduced pressure
  17. customto give a residue, which
  18. custompurified

出典と根拠

ORDレコード
ord-4bb0fe2e30a74f4d8e517ce488619c4d
出典データセット
uspto-grants-2015_08
特許番号
US09095581B2

反応ノート

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