Methanol → 4-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide

HRID 421780Notes

Reaction equation

HRID 421780 reaction equation
[NH2:1][C@@H:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH2:3][OH:4].[CH2:11]1[N:16]([C:17]([C:19]2[CH:24]=[CH:23][C:22]([S:25](Cl)(=[O:27])=[O:26])=[CH:21][CH:20]=2)=[O:18])[CH2:15][CH2:14][N:13]2[CH2:29][CH2:30][CH2:31][C@H:12]12.C(=O)([O-])[O-].[Na+].[Na+].CO>ClCCl.CN(C)C=O>[CH2:11]1[N:16]([C:17]([C:19]2[CH:20]=[CH:21][C:22]([S:25]([NH:1][C@@H:2]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:3][OH:4])(=[O:27])=[O:26])=[CH:23][CH:24]=2)=[O:18])[CH2:15][CH2:14][N:13]2[CH2:29][CH2:30][CH2:31][C@H:12]12

Participants

6

Reactant 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 1347972-Amino-2-phenylethan-1-olHCID 866439254-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonyl chloride

Product 1

HCID 468525944-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-[(1S)-2-hydroxy-1-phenylethyl]benzenesulfonamide

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

Then (S)-2-amino-2-phenylethanol (0.494 g, 3.6 mmol) in dichloromethane/N,N-dimethylformamide (5:1, 40 mL) was added to the crude 4-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]benzenesulfonyl chloride. The mixture was stirred at room temperature for 3 days, then sodium carbonate (0.21 g, 2 mmol) and methanol (10 mL) were added. The mixture was stirred for an additional 30 minutes, then the reaction mixture was filtered, and the filtrate was concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/methanol=10:1) to give the titled compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.35 (m, 1H), 1.60-2.10 (m, 6H), 2.90-3.20 (m, 4H), 3.30-3.50 (m, 3H), 4.30 (m, 1H), 4.50 (m, 1H), 4.85 (m, 1H), 7.10 (m, 5H), 7.30 (m, 2H), 7.61 (m, 2H), 8.30 (br s, 1H); MS (ESI) m/z 430 (M+H)+.

Workup

  1. stirringThe mixture was stirred for an additional 30 minutes
  2. filtrationthe reaction mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by chromatography on silica gel (ethyl acetate/methanol=10:1)

Sources & evidence

ORD record
ord-da0bca42e8404b8badef1a20e14b742f
Source dataset
uspto-grants-2012_01
Patent number
US08101614B2

Reaction notes

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