1,1'-Carbonyldiimidazole → HCID 66589535, compound

HRID 588035Notes

Reaction equation

HRID 588035 reaction equation
CS(O)(=O)=O.[NH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH:18]1[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]1=[O:25])[CH2:11]2.C1N=CN([C:31]([N:33]2C=N[CH:35]=[CH:34]2)=[O:32])C=1.[Si:38]([O:45][C:46]1[CH:52]=CC(N)=[CH:48][C:47]=1[CH3:53])([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39]>CN(C=O)C>[Si:38]([O:45][C:46]1[CH:52]=[CH:35][C:34]([NH:33][C:31]([NH:6][CH2:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH:18]2[CH2:23][CH2:22][C:21](=[O:24])[NH:20][C:19]2=[O:25])[CH2:11]3)=[O:32])=[CH:48][C:47]=1[CH3:53])([C:41]([CH3:42])([CH3:43])[CH3:44])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 18542390HCID 18542390, compoundHCID 866307653-(5-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate

Product 1

HCID 66589535HCID 66589535, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione methanesulfonate (0.74 g, 2.0 mmol) and CDI (0.32 g, 2.0 mmol) in DMF (30 mL) was stirred at room temperature for 3 h, and then the product from Step 2 (0.47 g, 2.0 mmol) was added. The mixture was heated to 70° C. for 30 h. Then, the mixture was cooled to room temperature and quenched with 1N HCl (30 mL), resulting in solid precipitate. This solid was purified by chromatography on a silica gel column, using a methylene chloride-methanol gradient, and providing 0.59 g of 1-(4-(tert-butyldimethylsilyloxy)-3-methylphenyl)-3-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)urea as an off-white solid, in 55% yield; 1H NMR (DMSO-d6) δ 0.16 (s, 6H), 0.97 (s, 9H), 1.88-2.06 (m, 1H), 2.10 (s, 3H), 2.25-2.47 (m, 1H), 2.53-2.70 (m, 1H), 2.80-3.02 (m, 1H), 4.31 (d, J=17.4 Hz, 1H), 4.36-4.52 (m, 3H), 5.11 (dd, J=4.9, 13.2 Hz, 1H), 6.51-6.74 (m, 2H), 7.08 (dd, J=2.5, 8.6 Hz, 1H), 7.18 (d, J=2.3 Hz, 1H), 7.43 (d, J=7.7 Hz, 1H), 7.50 (s, 1H), 7.69 (d, J=7.7 Hz, 1H), 8.35 (s, 1H), 10.98 (s, 1H).

Workup

  1. temperatureThe mixture was heated to 70° C. for 30 h
  2. temperatureThen, the mixture was cooled to room temperature
  3. customquenched with 1N HCl (30 mL)
  4. customresulting in solid precipitate
  5. customThis solid was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-cbe51a82890d4beea0716ecc5d65f0d7
Source dataset
uspto-grants-2016_01
Patent number
US09227954B2

Reaction notes

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