Sodium Iodide → 7-(3,5-Dichloro-benzyl)-5-methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one

HRID 853704Notes

Reaction equation

HRID 853704 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[CH2:13][NH:14][C:15](=[O:16])[C:11]=2[C:10]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[N:8]2.[H-].[Na+].[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([Cl:38])[CH:37]=1)[CH2:33]Cl.[I-].[Na+]>CN(C)C=O.C(O)(=O)C>[Cl:29][C:30]1[CH:31]=[C:32]([CH:35]=[C:36]([Cl:38])[CH:37]=1)[CH2:33][N:14]1[C:15](=[O:16])[C:11]2[C:10]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)=[C:9]3[C:4]([CH:5]=[CH:6][CH:7]=[N:8]3)=[C:3]([O:2][CH3:1])[C:12]=2[CH2:13]1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 1378803,5-Dichlorobenzyl chlorideHCID 589287845-Methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one

Product 1

HCID 589288867-(3,5-Dichloro-benzyl)-5-methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-oneYield 40%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 304 (17 mg, 0.049 mmol) was dissolved in dimethylformamide (0.3 ml) and cooled to 0° C. After adding sodium hydride (2.5 mg, 0.064 mmol), the reaction was stirred for 5 minutes at 0° C. 3,5-Dichlorobenzylchloride (11.5 mg, 0.059 mmol) and a catalytic amount of sodium iodide were then added. The reaction mixture was warmed to room temperature and stirred at room temperature for 30 minutes. It was then cooled to 0° C., acidified with acetic acid (0.030 ml), and concentrated in vacuo. The resulting residue was diluted with ethyl acetate, washed twice with water, once with brine, and concentrated in vacuo. The residue was purified by silica gel chromatography (99/1-ethyl acetate/acetic acid) to afford 7-(3,5-dichloro-benzyl)-5-methoxy-9-(4-methoxy-benzyloxy)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 307 (7 mg, 40%). 1H NMR (CDCl3) δ 9.0 (dd, 1H), 8.40 (dd, 1H), 7.60 (d, 2H), 7.55 (m, 1H), 7.20 (m, 3H), 6.80 (d, 2H), 5.60 (s, 2H), 4.75(s, 2H), 4.40 (s, 2H), 3.95 (s, 3H), 3.75 (s, 3H). MS: 509.1 (M+1).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred at room temperature for 30 minutes
  3. temperatureIt was then cooled to 0° C.
  4. concentrationconcentrated in vacuo
  5. additionThe resulting residue was diluted with ethyl acetate
  6. washwashed twice with water, once with brine
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (99/1-ethyl acetate/acetic acid)

Sources & evidence

ORD record
ord-90e5e5f62d1f4a84834f831bcaf74bca
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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