Sodium hydride → (+/-)-2a-[(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione

HRID 551084Notes

Reaction equation

HRID 551084 reaction equation
[NH:1]1[C:11]2[C:12]3[CH:3]([CH2:4][C:5](=[O:13])[NH:6][C:7]=3[CH:8]=[CH:9][CH:10]=2)[C:2]1=[O:14].[H-].[Na+].Br[CH2:18][N:19]1[C:23](=[O:24])[C:22]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:21]2[C:20]1=[O:29]>CN(C=O)C>[O:29]=[C:20]1[C:21]2[C:22](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:24])[N:19]1[CH2:18][C:3]12[C:2](=[O:14])[NH:1][C:11]3[C:12]1=[C:7]([CH:8]=[CH:9][CH:10]=3)[NH:6][C:5](=[O:13])[CH2:4]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 792441H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)-2×HCID 57663743(+/-)-2a,5-Dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione2×

Product 1

HCID 67173953(+/-)-2a-[(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (±)-2a,5-dihydropyrrolo[4,3,2-de]quinoline-2,4(1H,3H)-dione (2.00 g, 10.6 mmol, described in Intermediate 18) in degassed DMF (30 mL) at 0° C. was added sodium hydride (468 mg of a 60% dispersion in mineral oil, 11.7 mmol). The mixture was stirred for 10 min, then N-(bromomethyl)phthalimide (2.55 g, 10.6 mmol) was added and stirring was continued for 2 h. An additional portion of N-(bromomethyl)phthalimide (500 mg) was added and stirring was continued for 1 h. The reaction mixture was quenched with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 90:10, to give the title compound. MS: m/z=348 (M+1).

Workup

  1. stirringstirring
  2. waitwas continued for 2 h
  3. stirringstirring
  4. waitwas continued for 1 h
  5. customThe reaction mixture was quenched with saturated aqueous NaHCO3 (100 mL)
  6. extractionextracted with EtOAc (3×50 mL)
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography
  11. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-d69040fcd4db4064a3a6ad29bc7ac16b
Source dataset
uspto-grants-2011_05
Patent number
US07947677B2

Reaction notes

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