Water → racemic 8-(1-benzenesulfonylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

HRID 546715Notes

Reaction equation

HRID 546715 reaction equation
[C:1]1([S:7](Cl)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15](/[CH:25]=[CH:26]/[C:27]2[N:41]=[C:30]3[CH:31]([CH:35]4[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]4)[CH2:32][CH2:33][CH2:34][N:29]3[N:28]=2)[CH:16]=[CH:17][C:18]=1[N:19]1[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]1.O.C(OCC)(=O)C>C(Cl)Cl>[C:1]1([S:7]([N:38]2[CH2:39][CH2:40][CH:35]([CH:31]3[CH2:32][CH2:33][CH2:34][N:29]4[N:28]=[C:27](/[CH:26]=[CH:25]/[C:15]5[CH:16]=[CH:17][C:18]([N:19]6[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]6)=[C:13]([O:12][CH3:11])[CH:14]=5)[N:41]=[C:30]34)[CH2:36][CH2:37]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7369Benzenesulfonyl chlorideHCID 8857Ethyl AcetateHCID 668394842-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 66839435racemic 8-(1-benzenesulfonylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TEA (20 μl) and benzenesulfonyl chloride (8 μl) were added to a solution of racemic 2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-8-(piperidin-4-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine obtained in Examples 118 and 119 (20 mg) in methylene chloride (1 ml), and the reaction solution was stirred at room temperature for 40 minutes. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was sequentially washed with a saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 24 mg of racemic 8-(1-benzenesulfonylpiperidin-4-yl)-2-{(E)-2-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]vinyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine. Then, the racemate was separated by CHIRALCEL™ OD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: ethanol) to obtain the title optically active compound with a retention time of 24 minutes and positive optical rotation (7.3 mg; 100% ee) and the title optically active compound with a retention time of 29 minutes and negative optical rotation (7.4 mg; >98% ee).

Workup

  1. customthe organic layer was separated
  2. washThe organic layer was sequentially washed with a saturated sodium bicarbonate solution and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5126ced990ac42f799921d7e2e6d42d0
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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