Sodium Carbonate → (8aR)-2-{[3-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}carbonyl)phenyl]sulfonyl}octahydropyrrolo[1,2-a]pyrazine

HRID 400516

Reaction equation

HRID 400516 reaction equation
Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8](Cl)=[O:9])(=[O:4])=[O:3].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:41]1[NH:46][CH2:45][CH2:44][N:43]2[CH2:47][CH2:48][CH2:49][C@H:42]12>ClCCl.CO>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH:21]([C:18]2[CH:17]=[CH:16][C:15]([F:14])=[CH:20][CH:19]=2)[N:22]2[CH2:23][CH2:24][N:25]([C:8]([C:7]3[CH:6]=[C:5]([S:2]([N:46]4[CH2:45][CH2:44][N:43]5[CH2:47][CH2:48][CH2:49][C@@H:42]5[CH2:41]4)(=[O:4])=[O:3])[CH:13]=[CH:12][CH:11]=3)=[O:9])[CH2:26][CH2:27]2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 77671Benzoyl chloride, 3-(chlorosulfonyl)-HCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 7004239(8aR)-Octahydropyrrolo(1,2-a)pyrazine

Product 1

HCID 46852132(8aR)-2-{[3-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}carbonyl)phenyl]sulfonyl}octahydropyrrolo[1,2-a]pyrazine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 3-(chlorosulfonyl)benzoyl chloride (0.359 g, 1.5 mmol) in anhydrous dichloromethane (40 mL) was added 1-(bis(4-fluorophenyl)methyl)piperazine (0.433 g, 1.5 mmol) in dichloromethane (4 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.64 g, 6 mmol) was added. The mixture was stirred at room temperature overnight. Then (R)-octahydropyrrolo[1,2-a]pyrazine (0.208 g, 1.65 mmol) was added. The mixture was stirred at reflux for 20 minutes, and then at room temperature for 3 days. Methanol (5 mL) was added, the mixture was stirred for 20 minutes, then filtered, and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/methanol=20:1) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.09 (m, 1H), 1.55 (m, 2H), 1.72 (m, 1H), 1.90 (m, 4H), 2.10 (m, 1H), 2.20-2.50 (m, 6H), 2.90 (m, 2H), 3.58-3.78 (m, 4H), 4.42 (s, 1H), 7.12 (m, 4H), 7.42 (m, 4H), 7.71 (m, 3H), 7.80 (m, 1H); MS (ESI) m/z 581 (M+H)+.

Workup

  1. stirringThe mixture was stirred
  2. temperatureat reflux for 20 minutes
  3. waitat room temperature for 3 days
  4. stirringthe mixture was stirred for 20 minutes
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (ethyl acetate/methanol=20:1)

Sources & evidence

ORD record
ord-8b44502eb46a42f4925912466272f80e
Source dataset
uspto-grants-2014_06
Patent number
US08741899B2

Linked notes

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