Acetonitrile → (2'R,6'S)-1'-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2';6',2'']terpyridine

HRID 1784178Notes

Reaction equation

HRID 1784178 reaction equation
[CH2:1]([N:8]1[CH2:12][C:11]([CH2:13][CH2:14]OS(C)(=O)=O)=[CH:10][NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:21]1([CH3:29])[CH2:26][CH2:25][CH2:24][C:23]([CH3:28])(C)[NH:22]1.[CH3:30][C:31]#[N:32]>>[CH2:1]([N:8]1[CH2:12][C:11]([CH2:13][CH2:14][N:22]2[C@H:21]([C:29]3[C:11]([CH3:12])=[CH:10][CH:30]=[CH:31][N:32]=3)[CH2:26][CH2:25][CH2:24][C@@H:23]2[C:28]2[C:4]([CH3:5])=[CH:3][CH:2]=[CH:1][N:8]=2)=[CH:10][NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 130352,2,6,6-TetramethylpiperidineHCID 86597121methanesulfonic acid 2-(2-benzyl-1H-pyrazol-4-yl)-ethyl ester

Product 1

HCID 86597120(2'R,6'S)-1'-[2-(2-benzyl-1 H-pyrazol-4-yl)-ethyl]-3,3''-dimethyl-1',2',3',4',5',6'-hexahydro-[2,2';6',2'']terpyridineYield 93%

Procedure

A mixture of (2′R,6′S)-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2′]terpyridine (0.320 g, 1.20 mmol), methanesulfonic acid 2-(2-benzyl-1H-pyrazol-4-yl)-ethyl ester (0.540 g, 1.60 mmol) and 2,2,6,6-tetramethylpiperidine (0.255 g, 1.80 mmol) in CH3CN (5 mL) was stirred and heated at reflux overnight. The solvent was then removed, water (20 mL) was added, and the mixture was extracted with CH2Cl2 (3×20 mL). The extracts were combined and dried over Na2SO4. After filtration the solvent was removed by evaporation under vacuum, and the residue was purified by flash chromatography on a silica gel column (500:15:1 CH2Cl2/CH3OH/NH4OH), affording (2′R,6′S)-1′-[2-(2-benzyl-1H-pyrazol-4-yl)-ethyl]-3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine as a pale yellow oil (0.420 g, 93%).

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. customThe solvent was then removed
  4. additionwater (20 mL) was added
  5. extractionthe mixture was extracted with CH2Cl2 (3×20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed by evaporation under vacuum
  9. customthe residue was purified by flash chromatography on a silica gel column (500:15:1 CH2Cl2/CH3OH/NH4OH)

Sources & evidence

ORD record
ord-d81f1c07f8c244968da51f028cde2d6d
Source dataset
uspto-grants-2009_03
Patent number
US07501518B2

Reaction notes

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