Methyl iodide → 8-bromo-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

HRID 1486913Notes

Reaction equation

HRID 1486913 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:12][C:13](=[O:21])[N:14]([CH:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:5]=3[C:4]=2[CH:3]=1.[OH-].[Na+].[CH3:24]I>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CC1OCCC1>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:24])[C:13](=[O:21])[N:14]([CH:15]4[CH2:16][CH2:17][O:18][CH2:19][CH2:20]4)[C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 1185026328-bromo-1-(oxan-4-yl)-3H-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 1185234078-bromo-3-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-oneYield 257.5%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent2×

Conditions

Temperature
45 °C

Procedure

On a larger scale, 8-bromo-1-(oxan-4-yl)-3H-imidazo[4,5-c]quinolin-2-one (1300 g, 3.73 mol) was charged to the vessel along with tetrabutylammonium bromide (130 g, 0.40 mol) and 2-MeTHF (20.8 L). A solution of NaOH (240 g, 6.00 mol) in water (20.8 L) was then added over 5 minutes with an observed exotherrn from 18-24° C. The biphasic mixture was heated to 42-48° C. before the addition of methyl iodide (465 mL, 7.47 mol) as a solution in 2-MeTHF (930 mL). The reaction was stirred at 45° C. for 17 h at which point HPLC analysis showed 2.9% starting material and 97.1% product. The reaction mixture was combined with that of the other large scale batches for concentration in vacuo. The resulting aqueous suspension was then returned to the vessel and slurried for 1 h with the product material obtained from the development batches combined at this point. The product was then isolated by filtration, washing with water (2×12 L) before oven drying under vacuum at 40° C. In total 3479 g of 8-bromo-3-methyl-1-(oxan-4-yl)imidazo[5,4-c]quinolin-2-one was isolated. Analytical data was consistent with that obtained from previous batches.

Workup

  1. concentrationfor concentration in vacuo
  2. waitslurried for 1 h with the product material
  3. customobtained from the development batches
  4. customThe product was then isolated by filtration
  5. washwashing with water (2×12 L) before oven
  6. customdrying under vacuum at 40° C

Sources & evidence

ORD record
ord-d66caba335124da2b13a710ab0350668
Source dataset
uspto-grants-2016_08
Patent number
US09428503B2

Reaction notes

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