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

HRID 421774Notes

Reaction equation

HRID 421774 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 781249(6S)-1,4-Diazabicyclo(4.3.0)nonane

Product 1

HCID 46852288(8aS)-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 (0.474 g, 1.981 mmol) in anhydrous dichloromethane (40 mL) was added 1-(bis(4-fluorophenyl)methyl)piperazine (0.571 g, 1.981 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 (S)-octahydropyrrolo[1,2-a]pyrazine (0.250 g, 1.981 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 (400 MHz, DMSO-d6) δ ppm 1.07 (m, 1H), 1.55 (m, 2H), 1.71 (m, 1H), 1.95 (m, 4H), 2.08 (m, 1H), 2.28 (m, 3H), 2.39 (m, 3H), 2.85 (m, 1H), 2.92 (m, 1H), 3.57 (m, 2H), 3.74 (m, 2H), 4.45 (s, 1H), 7.13 (m, 4H), 7.45 (m, 4H), 7.66 (s, 1H), 7.70 (m, 2H), 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-5f92f0f853ad4f1cb29a5cfb9763bde4
Source dataset
uspto-grants-2012_01
Patent number
US08101614B2

Reaction notes

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