2-Fluoroaniline → 4-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

HRID 400520

Reaction equation

HRID 400520 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([S:12](Cl)(=[O:14])=[O:13])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:16]1[NH:21][CH2:20][CH2:19][N:18]2[CH2:22][CH2:23][CH2:24][C@@H:17]12.C(=O)([O-])[O-].[Na+].[Na+].[F:31][C:32]1[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=1[NH2:34]>ClCCl.CO>[Cl:1][C:2]1[C:3]([C:4]([N:21]2[CH2:20][CH2:19][N:18]3[CH2:22][CH2:23][CH2:24][C@H:17]3[CH2:16]2)=[O:5])=[CH:7][C:8]([S:12]([NH:34][C:33]2[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=2[F:31])(=[O:14])=[O:13])=[C:9]([F:11])[CH:10]=1

Participants

7

Reactant 4

HCID 95842-FluoroanilineHCID 10340Sodium Carbonate2×HCID 781249(6S)-1,4-Diazabicyclo(4.3.0)nonaneHCID 866439242-Chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride

Product 1

HCID 468524404-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent4×

Procedure

To crude 2-chloro-5-(chlorosulfonyl)-4-fluorobenzoyl chloride (4 mmol) in anhydrous dichloromethane (100 mL) was added (S)-octahydropyrrolo[1,2-a]pyrazine (0.505 g, 4 mmol) in dichloromethane (10 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.933 g, 8.8 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration in vacuo, and 2-fluoroaniline (4.44 g, 40 mmol) in dichloromethane (30 mL) was added. The mixture was stirred at room temperature for 4 days. At that time, sodium carbonate (0.42 g, 4 mmol) and methanol (20 mL) were added, the mixture was stirred for 30 minutes, then filtered, and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate, then methanol/ethyl acetate=1:15) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.20-1.38 (m, 1H), 1.60-2.20 (m, 7H), 2.80-3.40 (m, 4H), 4.40-4.60 (m, 1H), 7.20 (m, 4H), 7.60 (m, 1H), 7.88 (m, 1H), 10.60 (br s, 1H); MS (ESI) m/z 456 (M+H)+.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at room temperature for 4 days
  3. stirringthe mixture was stirred for 30 minutes
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate

Sources & evidence

ORD record
ord-6e875489de3d4759b43dbb3d08b1ff41
Source dataset
uspto-grants-2014_06
Patent number
US08741899B2

Linked notes

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