Potassium Carbonate → HCID 49848787, compound

HRID 1714847Notes

Reaction equation

HRID 1714847 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[CH2:15][C:14]3[C:9](=[C:10]([CH3:23])[CH:11]=[C:12]([C:16]4[N:20]=[C:19]([CH2:21]Cl)[O:18][N:17]=4)[CH:13]=3)[C:8]2=[O:24])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].C(OC([N:40]1[CH2:45][CH2:44][NH:43][C@H:42]([CH3:46])[CH2:41]1)=O)(C)(C)C>CC#N.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:15][C:14]3[C:9](=[C:10]([CH3:23])[CH:11]=[C:12]([C:16]4[N:20]=[C:19]([CH2:21][N:43]5[CH2:44][CH2:45][NH:40][CH2:41][CH:42]5[CH3:46])[O:18][N:17]=4)[CH:13]=3)[C:8]2=[O:24])=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2756811(R)-1-Boc-3-methylpiperazineHCID 59465460HCID 59465460, compound

Product 1

HCID 49848787HCID 49848787, compoundYield 39.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(4-chlorobenzyl)-5-(5-chloromethyl-[1,2,4]oxadiazol-3-yl)-7-methyl-2,3-dihydroisoindol-1-one (37 mg, 0.0952 mmol) in MeCN (4 mL) was added K2CO3 (39 mg, 0.286 mmol) and (3R)-3-methylpiperazine-1-carboxylic acid tert-butyl ester (38 mg, 0.190 mmol). The mixture was heated at 70° C. overnight, then diluted with water and extracted with EtOAc. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated to a yellow oil. This residue was dissolved in 1:1 TFA/CH2Cl2 for 30 minutes, then the reaction mixture was concentrated and basified with NaHCO3 to pH 9-10. The product was extracted with CH2Cl2. The organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography on silica (1% 2M NH3 in MeOH/CH2Cl2) to provide 2-(4-chlorobenzyl)-7-methyl-5-[5-(2-methylpiperazin-1-ylmethyl)-[1,2,4]oxadiazol-3-yl]-2,3-dihydroisoindol-1-one as a yellow oil (17 mg). 1H NMR (300 MHz, CDCl3) δ 7.97 (s, 1H), 7.93 (s, 1H), 7.33 (d, 2H), 7.26 (d, 2H), 4.77 (s, 2H), 4.29 (s, 2H), 4.17 (d, 1H), 4.06 (d, 1H), 2.83-3.04 (m, 4H), 2.83 (s, 3H), 2.50-2.61 (m, 3H), 1.19 (d, 3H).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil
  6. dissolutionThis residue was dissolved in 1:1 TFA/CH2Cl2 for 30 minutes
  7. concentrationthe reaction mixture was concentrated
  8. extractionThe product was extracted with CH2Cl2
  9. washThe organic phase was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by column chromatography on silica (1% 2M NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-93cbeffe330c416d988e21f171acded7
Source dataset
uspto-grants-2010_09
Patent number
US07799792B2

Reaction notes

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