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

HRID 505881Notes

Reaction equation

HRID 505881 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 2.0 mmol of LiAlH4 was again added. The reaction was refluxed for an additional 3 h, 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. temperatureThe reaction was refluxed for an additional 3 h
  3. customThe reaction was quenched by the sequential addition of water (5 drops), 10% NaOH (5 drops), and water (5 drops)
  4. filtrationThe mixture was filtered through Celite
  5. customevaporated
  6. customthe crude mixture was chromatographed on silica in 98:2 chloroform-methanol

Sources & evidence

ORD record
ord-92377cd50c114fb39ccf53141558727c
Source dataset
uspto-grants-2010_08
Patent number
US07781587B2

Reaction notes

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