Triethylamine → 2-[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperdin-1-yl]ethyl}phenyl)ethyl]-1H-isoindole-1,3(2H)-dione

HRID 2383372Notes

Reaction equation

HRID 2383372 reaction equation
[CH:1]1([C:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:9]2[N:13]=[CH:12][N:11]([CH2:14][CH:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[N:10]=2)[OH:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][N:38]2[C:46](=[O:47])[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[C:39]2=[O:48])=[CH:32][CH:31]=1.C(N(CC)CC)C>C(#N)C>[CH:21]1([C@@:7]([OH:8])([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:9]2[N:13]=[CH:12][N:11]([CH2:14][CH:15]3[CH2:20][CH2:19][N:18]([CH2:28][CH2:29][C:30]4[CH:31]=[CH:32][C:33]([CH2:36][CH2:37][N:38]5[C:46](=[O:47])[C:45]6[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=6)[C:39]5=[O:48])=[CH:34][CH:35]=4)[CH2:17][CH2:16]3)[N:10]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 591459472-{2-[4-(2-Bromo-ethyl)-phenyl]-ethyl}-isoindole-1,3-dioneHCID 59145970cyclohexyl(phenyl)[1-(piperidin-4-ylmethyl)-1H-1,2,4-triazol-3-yl]methanol

Product 1

HCID 591459622-[2-(4-{2-[4-({3-[(R)-cyclohexyl(hydroxy)phenylmethyl]-1H-1,2,4-triazol-1-yl}methyl)piperdin-1-yl]ethyl}phenyl)ethyl]-1H-isoindole-1,3(2H)-dioneYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

Cyclohexyl-phenyl-(1-piperidin-4-ylmethyl-1H-[1,2,4]triazol-3-yl)-methanol (Preparation 4, 8.2 g, 2.98 mmol), 2-{2-[4-(2-Bromo-ethyl)-phenyl]-ethyl}-isoindole-1,3-dione (Preparation 11, 7.56 g, 21.1 mmol), and triethylamine (13.3 ml, 95.9 mmol) were dissolved in acetonitrile (100 ml). After stirring at 90° C. for 48 hours the solvent was removed in vacuo, and the residue partitioned between dichloromethane (200 ml) and water (200 mL). The organic layer was separated, dried over magnesium sulphate, filtered and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (98:2:0.2, by volume) and the resulting material then triturated in tert-butyl methyl ether to furnish title compound as a clear solid in 28% yield, 3.4 g.

Workup

  1. customwas removed in vacuo
  2. customthe residue partitioned between dichloromethane (200 ml) and water (200 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane
  8. custommethanol:880 ammonia (98:2:0.2, by volume) and the resulting material then triturated in tert-butyl methyl ether

Sources & evidence

ORD record
ord-b91b556d3058423e8d404701653ad814
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

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