Pyridine → 2-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 2204293ノート

反応式

HRID 2204293 の反応式
CS(Cl)(=O)=O.[CH2:6]([O:8][C:9]([C:11]1[CH:15]=[CH:14][N:13]([CH:16]([CH3:18])[CH3:17])[C:12]=1[CH:19]([C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[CH3:28])O)=[O:10])[CH3:7].N1C=CC=CC=1.[Cl:35][C:36]1[C:37]([F:43])=[C:38]([NH2:42])[CH:39]=[CH:40][CH:41]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl.O1CCOCC1.CCOC(C)=O>[CH2:6]([O:8][C:9]([C:11]1[CH:15]=[CH:14][N:13]([CH:16]([CH3:18])[CH3:17])[C:12]=1[CH:19]([NH:42][C:38]1[CH:39]=[CH:40][CH:41]=[C:36]([Cl:35])[C:37]=1[F:43])[C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:22]=1[CH3:28])=[O:10])[CH3:7]

参加物

9

反応物 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 750143-Chloro-2-fluoroanilineHCID 867030962-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester

生成物 1

HCID 867030952-[(3-chloro-2-fluoro-phenylamino)-(4-chloro-2-methyl-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

Methanesulfonyl chloride (10.62 mmol) was added to a mixture of 2-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid ethyl ester (Step A4) (4.09 mmol), pyridine (14.01 mmol) and DMAP (1.226 mmol) in CH2Cl2 (70 mL). After stirring for 20 h, the reaction mixture was diluted with CH2Cl2 and washed with a saturated aqueous solution of NH4Cl (2×). The combined aqueous phases were back-extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered and concentrated. A mixture of the crude intermediate and 3-chloro-2-fluoro-phenylamine [2106-04-9] (11.64 mmol) in dioxane (90 mL) was stirred at 90° C. for 11 h. After cooling to rt, the reaction mixture was diluted with EtOAc and successively washed with 10% w/w aqueous citric acid and brine. The combined aqueous phases were back-extracted with EtOAc. The combined organic phases were dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a yellow solid. tR: 9.08 min (HPLC 2); ESI-MS: tR=1.54 min, [M]+318/320 (i.e. fragmented pyrrolium ion) (LC-MS 1); TLC: Rf=0.45 (1:4 EtOAc/hexanes).

後処理

  1. washwashed with a saturated aqueous solution of NH4Cl (2×)
  2. extractionThe combined aqueous phases were back-extracted with CH2Cl2
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringwas stirred at 90° C. for 11 h
  7. washsuccessively washed with 10% w/w aqueous citric acid and brine
  8. extractionThe combined aqueous phases were back-extracted with EtOAc
  9. dry with materialThe combined organic phases were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified

出典と根拠

ORDレコード
ord-35ac580c30dd4e578bb781a72244e3c4
出典データセット
uspto-grants-2016_06
特許番号
US09365576B2

反応ノート

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