Methyl vinyl sulfone → 2-(3,4-dimethoxy-benzyl)-4-(2-methanesulfonyl-vinyl)-7-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione

HRID 42325

Reaction equation

HRID 42325 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C@@H:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH3:18])[CH2:13][CH2:12]2)=[C:7]2[C:3]=1[C:4](=[O:37])[N:5]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[C:6]2=[O:25].C([O-])(=O)C.[Na+].[CH3:43][S:44]([CH:47]=[CH2:48])(=[O:46])=[O:45]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CC(N(C)C)=O>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[O:33][CH3:34])[CH2:26][N:5]1[C:4](=[O:37])[C:3]2[C:7](=[C:8]([N:11]3[CH2:12][CH2:13][N:14]([C@@H:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH3:18])[CH2:15][CH2:16]3)[CH:9]=[CH:10][C:2]=2[CH:48]=[CH:47][S:44]([CH3:43])(=[O:46])=[O:45])[C:6]1=[O:25]

Participants

6

Reactant 3

HCID 19354Methyl vinyl sulfoneHCID 517045Sodium AcetateHCID 236274314-chloro-2-(3,4-dimethoxy-benzyl)-7-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione

Product 1

HCID 866143122-(3,4-dimethoxy-benzyl)-4-(2-methanesulfonyl-vinyl)-7-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dioneYield 19.4%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A 10 mL sealed tube was charged with Compound 10 (100.0 mg, 0.19 mmol), sodium acetate (22.0 mg, 0.27 mmol), bis(tri-t-butylphosphine)palladium (0) (13.0 mg, 0.03 mmol), methyl vinylsulfone (0.02 ml, 0.23 mmol), and dimethylacetamide (1.0 mL). The tube was charge with argon and sealed. The mixture was heated at 150° C. for 24 h. The mixture was cooled to room temperature and purified via flash chromatography (230-400 mesh silica gel 60, gradient 90:10-50:50 hexanes:ethyl acetate) to give 21.7 mg (19%) of Compound 62 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.44 (d, J=15.6, 1 H), 7.48-7.53 (m, 5 H), 7.01-7.08 (m, 3 H), 6.70-6.90 (m, 3 H), 4.64 (s, 2 H), 4.42 (q, J=6.9 Hz, 1 H), 3.94 (s, 3 H), 3.86 (s, 3 H), 3.33-3.80 (m, 8 H), 3.07 (s, 3 H), and 1.86 (d, J=6.7 Hz, 3 H); MS (ES+) 590 (M+1).

Workup

  1. customA 10 mL sealed tube
  2. additionThe tube was charge with argon
  3. customsealed
  4. temperatureThe mixture was cooled to room temperature
  5. custompurified via flash chromatography (230-400 mesh silica gel 60, gradient 90:10-50:50 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-301d8921e914497cb883c292be0327cb
Source dataset
uspto-grants-2013_09
Patent number
US08536174B2

Linked notes

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