Potassium Carbonate → 2-(3-{5-[4-(1,3-Dioxo-isoindol-2-yl)-butyl]-pyridin-2-yl}-propyl)-isoindole-1,3-dione

HRID 993243

Reaction equation

HRID 993243 reaction equation
[CH2:1]([N:5]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]1=[O:15])[CH2:2][CH:3]=[CH2:4].B1C2CCCC1CCC2.C([O-])([O-])=O.[K+].[K+].Br[C:32]1[CH:33]=[CH:34][C:35]([CH2:38][CH2:39][CH2:40][N:41]2[C:49](=[O:50])[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42]2=[O:51])=[N:36][CH:37]=1>C1COCC1.CN(C=O)C.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[O:15]=[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:13](=[O:14])[N:5]1[CH2:1][CH2:2][CH2:3][CH2:4][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][CH2:39][CH2:40][N:41]2[C:42](=[O:51])[C:43]3[C:48](=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:49]2=[O:50])=[N:36][CH:37]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 339432N-(3-Buten-1-yl)phthalimideHCID 184089632-[3-(5-Bromo-pyridin-2-yl)-propyl]-isoindole-1,3-dione

Product 1

HCID 184089852-(3-{5-[4-(1,3-Dioxo-isoindol-2-yl)-butyl]-pyridin-2-yl}-propyl)-isoindole-1,3-dioneYield 76.2%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 3-3 (9.1 g, 45.4 mmol) in degassed THF (50 mL) at 0° C. was added dropwise a solution of 9-BBN (110 mL of 0.5M in THF, 55 mmol) and the mixture stirred for 18 hours at ambient temperature. K2CO3 (10.8 g, 77.4 mmol) and 3-2 (5.0 g, 17.4 mmol) were added, followed by a premixed and aged (70° C. for 30 min) suspension of Pd(OAc)2 (1.2 g, 5.2 mmol) and DPPF (3.2 g, 5.6 mmol) in degassed DMF (50 mL). The resulting mixture was stirred for 18 hours at 70° C., cooled, diluted with ethyl acetate, washed with water and brine, dried over MgSO4, and concentrated. The residue was chromatographed on silica gel (40-50% EtOAc/hexane) to give 6.2 g of 3-4 as a white solid.

Workup

  1. additiona premixed
  2. stirringThe resulting mixture was stirred for 18 hours at 70° C.
  3. temperaturecooled
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel (40-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-9f0785b893714f97b5a4052808061b31
Source dataset
uspto-grants-2002_10
Patent number
US06472403B2

Linked notes

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