Methyl iodide → HCID 20654274, compound

HRID 1352700Notes

Reaction equation

HRID 1352700 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:27][N:16]2[CH2:17][CH2:18][N:19]([C:21]3[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[CH2:20][CH:15]2[CH2:14][CH2:13]1.[H-].[Na+].[CH3:30]I>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH3:30])[CH:6]=[C:5]2[CH2:11][CH:12]1[CH2:27][N:16]2[CH2:17][CH2:18][N:19]([C:21]3[N:22]=[CH:23][CH:24]=[CH:25][N:26]=3)[CH2:20][CH:15]2[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 20654273HCID 20654273, compound

Product 1

HCID 20654274HCID 20654274, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A flame-dried flask was charged with 0.103 g (0.28 mmol) of (7RS,9aSR)-7-(5-fluoro-1H-indol-3-yl)methyl-2-(pyrimidin-2-yl)-2,3,4,6,7,8,9,9a-octahydro-1H-pyrido[1,2-a]pyrazine (Example 50), anhydrous DMF (1 mL) and 12 mg (0.30 mmol) of sodium hydride (60% oil dispersion). The suspension was treated with 0.019 mL (0.31 mmol) of methyl iodide and the mixture was heated at 50° C. for 16 h. The mixture was cooled to room temperature, concentrated in vacuo, and diluted with methylene chloride (25 mL) and water (25 mL), and the layers were separated. The organic phase was dried (sodium sulfate), filtered and evaporated to a solid residue. The solid was washed with ethyl acetate (2×), the ethyl acetate was evaporated to give 50 mg of the title compound. 1H NMR (CDCl3): δ 1.00–1.31 (m, 3H), 1.64–2.23 (m, 6H), 2.54–3.1 (m, 5H), 3.69 (s, 3H), 4.51–4.56 (m, 2H), 6.43 (dd, J=1 Hz, 1H), 6.83 (s, 1H), 6.93 (m, 1H), 7.15 (m, 2H), 8.27 (d, J=1 Hz, 2H). TLC Rf: 0.81 (90:10:1 methylene chloride:methanol:ammonium hydroxide).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. additiondiluted with methylene chloride (25 mL) and water (25 mL)
  4. customthe layers were separated
  5. dry with materialThe organic phase was dried (sodium sulfate)
  6. filtrationfiltered
  7. customevaporated to a solid residue
  8. washThe solid was washed with ethyl acetate (2×)
  9. customthe ethyl acetate was evaporated

Sources & evidence

ORD record
ord-0485570f4d504c8d930843f6a288bfa7
Source dataset
uspto-grants-2007_05
Patent number
US07220753B2

Reaction notes

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