Methyl iodide → 1-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-methoxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

HRID 445668Notes

Reaction equation

HRID 445668 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([N:8]2[C:20]3[C:19]4[CH:18]=[C:17]([C:21]5[CH:22]=[N:23][C:24]([CH2:27][OH:28])=[CH:25][CH:26]=5)[CH:16]=[CH:15][C:14]=4[N:13]=[CH:12][C:11]=3[N:10]([CH3:29])[C:9]2=[O:30])[C:5]([CH3:31])=[N:4]1)[CH3:2].[H-].[Na+].I[CH3:35]>CN(C=O)C>[CH2:1]([N:3]1[CH:7]=[C:6]([N:8]2[C:20]3[C:19]4[CH:18]=[C:17]([C:21]5[CH:22]=[N:23][C:24]([CH2:27][O:28][CH3:35])=[CH:25][CH:26]=5)[CH:16]=[CH:15][C:14]=4[N:13]=[CH:12][C:11]=3[N:10]([CH3:29])[C:9]2=[O:30])[C:5]([CH3:31])=[N:4]1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 498353111-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-hydroxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 596196291-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-methoxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-8-(6-hydroxymethyl-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 16.1, 28 mg, 0.068 mmol) in DMF (1 ml) was added NaH 55% (4 mg, 0.092 mmol) and the mixture was stirred for 20 min. Then iodomethane (0.006 ml, 0.096 mmol) was added and the RM was stirred again at rt for 30 min. After that, the RM was quenched with saturated aqueous NaHCO3 (20 ml) and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was dissolved in DMA and purified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35). The fractions containing products were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting suspension was filtered and the cake was washed with water, before being dried under high vacuum to give the title compound as a white solid. (HPLC: tR 2.30 min (Method A); M+H=429 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.98 (s, 1H), 8.63 (s, 1H), 8.20 (s, 1H), 8.15-8.10 (m, 1H), 7.98-7.93 (m, 1H), 7.92-7.87 (m, 1H), 7.58-7.53 (m, 1H), 7.49-7.44 (m, 1H), 4.54-4.50 (m, 2H), 4.23-4.15 (m, 2H), 3.58 (s, 3H), 3.37 (s, 3H), 1.95 (s, 3H), 1.32 (t, 3H))

Workup

  1. stirringthe RM was stirred again at rt for 30 min
  2. customAfter that, the RM was quenched with saturated aqueous NaHCO3 (20 ml)
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was dissolved in DMA
  9. custompurified directly by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 65:35)
  10. additionThe fractions containing products
  11. customwere collected together
  12. concentrationbefore being concentrated
  13. filtrationThe resulting suspension was filtered
  14. washthe cake was washed with water
  15. custombefore being dried under high vacuum

Sources & evidence

ORD record
ord-10bfb31116c140b880920ec5c9336317
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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