Tetrahydrofuran → 9,10-dimethoxy-13-methyl-8-prop-1-ynyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline

HRID 2381199Notes

Reaction equation

HRID 2381199 reaction equation
[CH3:1][O:2][C:3]1[C:23]2[CH2:22][NH+:10]3[CH2:11][CH2:12][C:13]4[C:18]([C:9]3=[C:8]([CH3:24])[C:7]=2[CH:6]=[CH:5][C:4]=1[O:25][CH3:26])=[CH:17][C:16]1[O:19][CH2:20][O:21][C:15]=1[CH:14]=4.[I-].[C:28]([Mg]Br)#[C:29][CH3:30].O1CCCC1>C(OCC)C>[CH3:1][O:2][C:3]1[C:23]2[CH:22]([C:28]#[C:29][CH3:30])[N:10]3[CH2:11][CH2:12][C:13]4[C:18]([C:9]3=[C:8]([CH3:24])[C:7]=2[CH:6]=[CH:5][C:4]=1[O:25][CH3:26])=[CH:17][C:16]1[O:19][CH2:20][O:21][C:15]=1[CH:14]=4

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 30165Iodide IonHCID 866474919,10-Dimethoxy-13-methyl-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-yliumHCID 178419101HCID 178419101, compound

Product 1

HCID 498060929,10-dimethoxy-13-methyl-8-prop-1-ynyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolineYield 61%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 9,10-dimethoxy-13-methyl-5,6-dihydro-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ylium; iodide (200 mg, 0.4 mmol) in anhydrous diethyl ether (5 mL) at 0° C. was added a solution of 1-propynylmagnesium bromide in tetrahydrofuran (0.5 M, 17 mL, 8.5 mmol) dropwise. After stirring at 0° C. for 30 min, the reaction was quenched by adding saturated aqueous ammonium chloride solution (20 mL). The mixture was extracted with diethyl ether (2×50 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was re-crystallized from diethyl ether to afford 9,10-dimethoxy-13-methyl-8-prop-1-ynyl-5,8-dihydro-6H-[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinoline (100 mg, 61%). LC/MS m/e calcd for C24H23NO4 (M+H)+: 390.46, observed: 390.2; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67 (d, J=1.52 Hz, 3 H) 2.22 (s, 3 H) 2.59-2.69 (m, 1 H) 2.89-2.99 (m, 1 H) 3.16-3.27 (m, 2 H) 3.81 (d, J=7.58 Hz, 6 H) 5.38 (d, J=1.77 Hz, 1 H) 6.04 (d, J=2.78 Hz, 2 H) 6.84 (s, 1 H) 6.96 (m, 2 H) 7.06 (s, 1 H).

Workup

  1. customthe reaction was quenched
  2. additionby adding saturated aqueous ammonium chloride solution (20 mL)
  3. extractionThe mixture was extracted with diethyl ether (2×50 mL)
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was re-crystallized from diethyl ether

Sources & evidence

ORD record
ord-ac529b86f1714bacb71226ed262e84cc
Source dataset
uspto-grants-2012_09
Patent number
US08258149B2

Reaction notes

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