4-(Trifluoromethyl)aniline → 4-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

HRID 400509

Reaction equation

HRID 400509 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH2:15]1[NH:20][CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@H:16]12.C(=O)([O-])[O-].[Na+].[Na+].[F:30][C:31]([F:40])([F:39])[C:32]1[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=1>ClCCl.CO>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([S:11]([NH:36][C:35]2[CH:37]=[CH:38][C:32]([C:31]([F:30])([F:39])[F:40])=[CH:33][CH:34]=2)(=[O:13])=[O:12])=[CH:7][C:3]=1[C:4]([N:20]1[CH2:19][CH2:18][N:17]2[CH2:21][CH2:22][CH2:23][C@@H:16]2[CH2:15]1)=[O:5]

Participants

7

Reactant 4

HCID 99644-(Trifluoromethyl)anilineHCID 10340Sodium Carbonate2×HCID 7004239(8aR)-Octahydropyrrolo(1,2-a)pyrazineHCID 545501992-Chloro-5-(chlorosulfonyl)benzoyl chloride

Product 1

HCID 468516554-chloro-3-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[4-(trifluoromethyl)phenyl]benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Procedure

To crude 2-chloro-5-(chlorosulfonyl)benzoyl chloride (2 mmol) in anhydrous dichloromethane (50 mL) was added (R)-octahydropyrrolo[1,2-a]pyrazine (0.252 g, 2 mmol) in dichloromethane (4 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.46 g, 4.4 mmol) was added. The mixture was stirred at room temperature overnight. Then dichloromethane was removed by concentration, and 4-(trifluoromethyl)aniline (3.22 g, 20 mmol) was added. The mixture was stirred at 70° C. overnight. Then sodium carbonate (0.21 g, 2 mmol) and methanol (5 mL) were added at room temperature. 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=1:10) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.30 (m, 1H), 1.55 (m, 1H), 1.70-2.00 (m, 4H), 2.60 (m, 2H), 2.80-3.50 (m, 4H), 4.40-4.60 (m, 1H), 7.30 (m, 2H), 7.62 (m, 2H), 7.82 (m, 3H), 11.00 (br s, 1H); MS (ESI) m/z 488 (M+H)+.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at 70° C. overnight
  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-24a5ad4037d141079fc06e5d0e9bcf33
Source dataset
uspto-grants-2014_06
Patent number
US08741899B2

Linked notes

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