1,1'-Carbonyldiimidazole → (2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanone

HRID 334989Notes

Reaction equation

HRID 334989 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:13]([O:20][C:21]1[CH:29]=[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:27]([C:38]([CH3:40])=[CH2:39])=[CH:26][C:22]=1[C:23](O)=[O:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:41][N:42]1[CH2:47][CH2:46][N:45]([CH2:48][C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][CH:57]=2)[CH2:54][NH:53][CH2:52]3)[CH2:44][CH2:43]1>CN(C=O)C>[CH2:13]([O:20][C:21]1[CH:29]=[C:28]([O:30][CH2:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:27]([C:38]([CH3:40])=[CH2:39])=[CH:26][C:22]=1[C:23]([N:53]1[CH2:52][C:51]2[C:55](=[CH:56][CH:57]=[C:49]([CH2:48][N:45]3[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]3)[CH:50]=2)[CH2:54]1)=[O:24])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 119558195-((4-Methylpiperazin-1-YL)methyl)isoindolineHCID 498640162,4-Bis(benzyloxy)-5-isopropenylbenzoic acid

Product 1

HCID 57990219(2,4-Bis-benzyloxy-5-isopropenyl-phenyl)-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindol-2-yl]-methanoneYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

1,1′-Carbonyldiimidazole (4.82 Kg, 29.8 mol) was added to a solution of 2,4-bis-benzyloxy-5-isopropenyl-benzoic acid (10.58 Kg, 28.3 mol, step 5) in DMF (21.2 L) at 25° C. After 20 mins at 25° C. a solution of 5-(4-Methyl-piperazin-1-ylmethyl)-2,3-dihydro-1H-isoindole (7.2 Kg, 31.1 mol, step 10) in DMF (7.2 L) maintaining a temperature below 35° C. and the solution stirred at 25° C. for a minimum of 12 h. The solid which had formed was removed by filtration, washed with isopropyl acetate (2×21.6 L) and dried at 35° C. to constant weight to give the title compound 8.7 Kg (77% yield, purity by hplc 97.5%).

Workup

  1. customThe solid which had formed
  2. customwas removed by filtration
  3. washwashed with isopropyl acetate (2×21.6 L)
  4. customdried at 35° C. to constant weight

Sources & evidence

ORD record
ord-a45a871cd4ed4ceaa8654f14d47aac14
Source dataset
uspto-grants-2014_11
Patent number
US08883790B2

Reaction notes

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