Sodium Iodide → 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 2383374Notes

Reaction equation

HRID 2383374 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][CH2:21]OS(C)(=O)=O)=[CH:16][CH:15]=1.[I-].[Na+].[CH:29]1([C:35]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)([C:37]2[N:41]=[CH:40][N:39]([CH2:42][CH:43]3[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[N:38]=2)[OH:36])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.C(N(C(C)C)CC)(C)C>C(#N)C.O>[CH:49]1([C@@:35]([OH:36])([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:37]2[N:41]=[CH:40][N:39]([CH2:42][CH:43]3[CH2:48][CH2:47][N:46]([CH2:21][CH2:20][C:17]4[CH:16]=[CH:15][C:14]([CH2:13][CH2:12][N:3]5[C:4](=[O:11])[C:5]6[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=6)[C:2]5=[O:1])=[CH:19][CH:18]=4)[CH2:45][CH2:44]3)[N:38]=2)[CH2:54][CH2:53][CH2:52][CH2:51][CH2:50]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 59145966Methanesulfonic acid 2-{4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-phenyl}-ethyl esterHCID 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 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

Methanesulfonic acid 2-{4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-phenyl}-ethyl ester (Preparation 35, 20.00 g, 53.56 mmol) was dissolved in acetonitrile (80 mL) and stirred at room temperature. Sodium iodide (16.06 g, 107.12 mmol) was added portionwise and the resulting slurry heated to 80° C. for 18 h. The reaction mixture was cooled to 50° C. and further acetonitrile (80 mL) was added. To this mixture was added cyclohexyl-phenyl-(1-piperidin-4-ylmethyl-1H-[1,2,4]triazol-3-yl)-methanol (Preparation 4, 15.87 g, 53.56 mmol) and diisopropylethylamine (9.79 mL, 56.24 mmol) and heating was continued for 6 hours, then allowed to cool to room temperature. Water (160 mL) was added and the resulting slurry stirred overnight at room temperature. The solid was collected by filtration and washed with acetonitrile (5×20 mL), then dried in vacuo at 45° C. for 8 hours to yield the title compound as a brown solid in 68% yield, 20.9 g,

Workup

  1. temperaturethe resulting slurry heated to 80° C. for 18 h
  2. temperatureThe reaction mixture was cooled to 50° C.
  3. temperatureheating
  4. temperatureto cool to room temperature
  5. stirringthe resulting slurry stirred overnight at room temperature
  6. filtrationThe solid was collected by filtration
  7. washwashed with acetonitrile (5×20 mL)
  8. customdried in vacuo at 45° C. for 8 hours

Sources & evidence

ORD record
ord-18b58d679d6f42b6a594322503302c98
Source dataset
uspto-grants-2012_09
Patent number
US08263623B2

Reaction notes

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