Methyl iodide → (6bR,10aS)-Ethyl 3-methyl-2-oxo-2,3,6b,7,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(9H)-carboxylate

HRID 350787Notes

Reaction equation

HRID 350787 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:13][N:12]2[C@H:14]3[CH2:19][CH2:18][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:16][C@H:15]3[C:10]3[C:11]2=[C:6]([CH:7]=[CH:8][CH:9]=3)[NH:5]1.I[CH3:26]>CCCCCC.CN(C)C=O>[CH3:26][N:5]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C@@H:15]4[CH2:16][N:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH2:18][CH2:19][C@@H:14]4[N:12]([C:11]=23)[CH2:13][C:4]1=[O:3]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 20578971ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

Product 1

HCID 21302625(6bR,10aS)-Ethyl 3-methyl-2-oxo-2,3,6b,7,10,10a-hexahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(9H)-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (900 mg of 60% dispersion in oil; 22.5 mmol) was washed with hexane, and suspended in anhydrous dimethylformamide (5 mL). The suspension was added to a stirred solution of ethyl (6bR,10aS)-2-oxo-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate (6.02 g, 20 mmol) in anhydrous dimethylformamide (50 mL) under nitrogen. After gas evolution had subsided, the mixture was cooled in ice-water bath and treated with iodomethane (3.55 g., 25 mmol). The mixture was stirred at room temperature for 1 h and then concentrated. The residue was treated with water and extracted with dichloromethane (2×) and the extract was washed with brine, dried over magnesium sulfate and evaporated to dryness to yield 5.48 g (87%) of ethyl (6bR,10aS)-3-methyl-2-oxo-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-carboxylate as a tan solid, m.p. 149–151° C. (dec.). [M+H] calc. 316; found 316. 1H NMR (CDCl3, 300 MHz) δ 1.28 (t, J=7.3 Hz, 3H), 1.85 to 1.93 (m, 1H), 2.65 to 2.82 (m, 1H), 3.08 to 3.25 (m, 1H), 3.25 to 3.40 (m, 1H), 3.30–3.50 (m, 1H), 3.34 (s, 3H), 3.42 (d, J=14.3 Hz, 1H), 3.85 to 4.0 (m, 1H), 4.02 (d, J=14.3 Hz, 1H, 4.15 (q, J=7.2 Hz, 4H), 6.76 (d, J=8.1 Hz, 1H), 6.83 (t, J=7.3 Hz, 1H), 6.90 (d, J=7.3 Hz, 1H). MS (CI): 316 (M+H+).

Workup

  1. concentrationconcentrated
  2. additionThe residue was treated with water
  3. extractionextracted with dichloromethane (2×)
  4. washthe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-7a96ef4fde8149118edcfe076ce01fb0
Source dataset
uspto-grants-2007_02
Patent number
US07183282B2

Reaction notes

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