Arc-111 → 8,9-Dimethoxy-2,3-methylenedioxy-5-[2-(N,N-dimethylamino)ethyl]-5,6-dihydro-dibenzo[c,h]1,6-naphthyridine

HRID 1825770Notes

Reaction equation

HRID 1825770 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:30][CH3:31])=[CH:5][C:6]2[C:15]3[C:10](=[C:11]4[CH:19]=[C:18]5[O:20][CH2:21][O:22][C:17]5=[CH:16][C:12]4=[N:13][CH:14]=3)[N:9]([CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[C:8](=O)[C:7]=2[CH:29]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:1][O:2][C:3]1[C:4]([O:30][CH3:31])=[CH:5][C:6]2[C:15]3[C:10](=[C:11]4[CH:19]=[C:18]5[O:20][CH2:21][O:22][C:17]5=[CH:16][C:12]4=[N:13][CH:14]=3)[N:9]([CH2:23][CH2:24][N:25]([CH3:26])[CH3:27])[CH2:8][C:7]=2[CH:29]=1

Participants

4

Reactant 2

HCID 9888428Arc-111HCID 21226445Aluminium lithium hydride2×

Product 1

HCID 221395198,9-Dimethoxy-2,3-methylenedioxy-5-[2-(N,N-dimethylamino)ethyl]-5,6-dihydro-dibenzo[c,h]1,6-naphthyridineYield 85.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8,9-dimethoxy-2,3-methylenedioxy-5-[2-(N,N-dimethylamino)ethyl]-5H-dibenzo[c,h]1,6-naphthyridin-6-one (160 mg, 0.38 mmol) in THF (650 mL) was added LiAlH4 (75 mg, 2.0 mmol), and the mixture was stirred under nitrogen at reflux. After 2 h, an additional 2.0mmol of LiAlH4 was again added. The reaction was refluxed for an additional 3h, then allowed to cool to room temperature. The reaction was quenched by the sequential addition of water (5 drops), 10% NaOH (5 drops), and water (5 drops). The mixture was filtered through Celite and evaporated, and the crude mixture was chromatographed on silica in 98:2 chloroform-methanol, to give 132 mg of the reduced product, in 85% yield; mp 271-273° C. (dec.); 1H NMR (CDCl3) δ 2.24 (s, 6H), 2.58 (t, 2H, J=6.8), 3.12 (t, 2H, J=6.8), 3.97 (s, 3H), 4.02 (s, 3H), 4.27 (s, 2H), 6.13 (s, 2H), 6.79 (s, 1H), 7.38 (s, 2H), 7.61 (s, 1H), 9.05 (s, 1H); 13C NMR (CDCl3) δ 46.0, 50.6, 51.2, 56.2, 26.3, 58.4, 99.6, 101.7, 105.7, 106.6, 110.0, 120.7, 123.1, 124.8, 131.1, 144.1, 146.9, 148.0, 149.0, 149.4, 149.8, 150.2; HRMS calcd for C23H25N3O4: 407.1845; found 407.1848.

Workup

  1. temperatureat reflux
  2. customThe reaction was quenched by the sequential addition of water (5 drops), 10% NaOH (5 drops), and water (5 drops)
  3. filtrationThe mixture was filtered through Celite
  4. customevaporated
  5. customthe crude mixture was chromatographed on silica in 98:2 chloroform-methanol

Sources & evidence

ORD record
ord-ed676cebe7dd45d5bf5a3fb683220799
Source dataset
uspto-grants-2006_05
Patent number
US07049315B2

Reaction notes

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