Pyridine → 5-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester

HRID 2204298Notes

Reaction equation

HRID 2204298 reaction equation
N1C=CC=CC=1.O(S(C)(=O)=O)S(C)(=O)=O.[CH3:16][O:17][C:18]([C:20]1[CH:24]=[C:23]([Br:25])[N:22]([CH:26]([CH3:28])[CH3:27])[C:21]=1[CH:29]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)O)=[O:19].[Cl:38][C:39]1[CH:40]=[C:41]([CH:43]=[CH:44][C:45]=1[F:46])[NH2:42]>CN(C1C=CN=CC=1)C.C(Cl)Cl.O.[Cl-].[Na+].O>[CH3:16][O:17][C:18]([C:20]1[CH:24]=[C:23]([Br:25])[N:22]([CH:26]([CH3:28])[CH3:27])[C:21]=1[CH:29]([NH:42][C:41]1[CH:43]=[CH:44][C:45]([F:46])=[C:39]([Cl:38])[CH:40]=1)[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)=[O:19]

Participants

8

Reactant 4

HCID 1049PyridineHCID 97083-Chloro-4-fluoroanilineHCID 81560Methanesulfonic anhydrideHCID 867031015-bromo-2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester

Product 1

HCID 867031005-bromo-2-[(3-chloro-4-fluoro-phenylamino)-(4-chloro-phenyl)-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 23713072Sodium chloride dihydrateSolvent2×

Procedure

Pyridine (5.59 mmol), DMAP (0.486 mmol) and then Ms2O (4.22 mmol) were added to a solution of 5-bromo-2-[(4-chloro-phenyl)-hydroxy-methyl]-1-isopropyl-1H-pyrrole-3-carboxylic acid methyl ester (step D3) (1.622 mmol) in CH2Cl2 (20 mL) and the reaction mixture was stirred at rt 17.5 h. The reaction mixture was diluted with H2O/brine and extracted with CH2Cl2 (3×). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was diluted with CH2Cl2 (20 mL) and 3-chloro-4-fluoroaniline [367-21-5] (1.865 mmol) was added and the mixture was stirred at rt for 20.5 h. The reaction mixture was diluted with H2O/brine and extracted with CH2Cl2 (3×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified using a RediSep® silica gel column to afford the title compound as a yellow foam. tR: 6.29 min (HPLC 1); ESI-MS: tR=1.57 min, [M+H]+ 513/515/517 (LC-MS 1); TLC: Rf=0.45 (1:6 EtOAc/heptanes).

Workup

  1. extractionextracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionwas added
  6. stirringthe mixture was stirred at rt for 20.5 h
  7. extractionextracted with CH2Cl2 (3×)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified

Sources & evidence

ORD record
ord-9d159acffc514c9badbe83e3c3bdbf3c
Source dataset
uspto-grants-2016_06
Patent number
US09365576B2

Reaction notes

Loading…