Methyl iodide → HCID 57752618, compound

HRID 226111Notes

Reaction equation

HRID 226111 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C@@H:26]([OH:28])[CH3:27])[C:20]=4[O:19][C:18]=3[CH3:29])=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].[H-].[Na+].[CH3:32]I>C1COCC1>[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([C:13]([C:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C@@H:26]([O:28][CH3:32])[CH3:27])[C:20]=4[O:19][C:18]=3[CH3:29])=[C:14]([CH3:16])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68856332HCID 68856332, compound

Product 1

HCID 57752618HCID 57752618, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (S)-1-{3-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-2-methyl-benzofuran-7-yl}-ethanol (0.19 g, 0.50 mmol) in THF (5 mL) is cooled to 0° C., treated with 60% NaH (23 mg, 0.56 mmol). The mixture is stirred at 0° C. for 30 min. CH3I (47 uL, 0.76 mmol) is added and the resulting mixture is stirred at 0° C. for 1 h and gradually warmed to rt. and stirred at rt overnight. The excess reagent is removed in vacuo. The residue is taked up with H2O (20 mL) and EtOAc (50 mL). It is washed with sat. NH4Cl (2×30 mL). The organic lay is dried with Na2SO4, filtered and concentrated. Purification of the crude material by chromatography gives the title compound (0.17 g, 0.41 mmol, 82%). 1H NMR (CDCl3): δ. 0.90 (t, J=7.5 Hz, 3H), 0.90 (t, J=7.5 Hz, 3H), 1.63 (d, J=4.0 Hz, 1.5H), 1.64 (d, J=4.0 Hz, 1.5H), 1.78-1.92 (m, 4H), 2.44 (s, 3H), 2.46 (s, 3H), 2.48 (s, 3H), 3.34-3.42 (m, 1H), 4.90-4.98 (m, 1H), 6.68 (s, 1H), 7.17-7.19 (m, 1H), 7.26-7.29 (m, 2H) ppm. ES-MS (m/z): calcd for C25H31N3O2 (M+H)+: 406.5. found: 406.2.

Workup

  1. stirringthe resulting mixture is stirred at 0° C. for 1 h
  2. temperaturegradually warmed to rt
  3. stirringand stirred at rt overnight
  4. customThe excess reagent is removed in vacuo
  5. washIt is washed with sat. NH4Cl (2×30 mL)
  6. dry with materialThe organic lay is dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude material by chromatography

Sources & evidence

ORD record
ord-b2d8e8278297427881d7c405eefb957d
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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