Benzoyl chloride → racemic 1-[4-(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]pyridin-8-yl)piperidin-1-yl]phenylmethanone

HRID 546714Notes

Reaction equation

HRID 546714 reaction equation
[OH-].[Na+].[C:3](Cl)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16](/[CH:26]=[CH:27]/[C:28]2[N:42]=[C:31]3[CH:32]([CH:36]4[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]4)[CH2:33][CH2:34][CH2:35][N:30]3[N:29]=2)[CH:17]=[CH:18][C:19]=1[N:20]1[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]1>C(Cl)Cl>[CH3:12][O:13][C:14]1[CH:15]=[C:16](/[CH:26]=[CH:27]/[C:28]2[N:42]=[C:31]3[CH:32]([CH:36]4[CH2:37][CH2:38][N:39]([C:4]5([CH:3]=[O:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH2:5]5)[CH2:40][CH2:41]4)[CH2:33][CH2:34][CH2:35][N:30]3[N:29]=2)[CH:17]=[CH:18][C:19]=1[N:20]1[CH:24]=[C:23]([CH3:25])[N:22]=[CH:21]1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 14798Sodium HydroxideHCID 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 87175012racemic 1-[4-(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]pyridin-8-yl)piperidin-1-yl]phenylmethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 1 N sodium hydroxide solution (0.5 ml) and benzoyl chloride (11 ul) 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 under ice-cooling for four hours. Methylene chloride was added to the reaction solution, and the organic layer was separated. The aqueous layer was reextracted with methylene chloride. The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 19 mg of racemic 1-[4-(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]pyridin-8-yl)piperidin-1-yl]phenylmethanone. Then, the racemate was separated by CHIRALPAK™ IB manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm; mobile phase: 50% ethanol-hexane) to obtain the title optically active compound with a retention time of 16 minutes and positive optical rotation (6.9 mg; 100% ee) and the title optically active compound with a retention time of 22 minutes and negative optical rotation (6.8 mg; >99% ee).

Workup

  1. temperaturecooling for four hours
  2. customthe organic layer was separated
  3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f39d47b124124e96b05540cc7f9f3df4
Source dataset
uspto-grants-2011_05
Patent number
US07935815B2

Reaction notes

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