Dimethylformamide → 8-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203609Notes

Reaction equation

HRID 2203609 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:17]=[CH:16][C:15]2[N:14]=[C:13]([NH2:18])[C:12]3[N:19]=[C:20]([CH2:25][O:26][CH3:27])[N:21]([CH2:22][CH2:23][CH3:24])[C:11]=3[C:10]=2[CH:9]=1.Br[CH2:29][CH2:30][CH2:31][Cl:32].CN(C)C=O>[Cl-].[Na+].O>[Cl:32][CH2:31][CH2:30][CH2:29][O:7][C:8]1[CH:17]=[CH:16][C:15]2[N:14]=[C:13]([NH2:18])[C:12]3[N:19]=[C:20]([CH2:25][O:26][CH3:27])[N:21]([CH2:22][CH2:23][CH3:24])[C:11]=3[C:10]=2[CH:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 80061-Bromo-3-chloropropaneHCID 10796Cesium carbonate2×HCID 689723708-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 689690038-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 37.4%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
50 °C

Procedure

Cesium carbonate (5.7 g, 17.4 mmol, 2 eq) was added to a mixture of 8-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (2.5 g, 8.7 mmol, 1 eq), prepared as described in Examples 523-550 Parts A-D, 1-bromo-3-chloropropane (0.94 mL, 9.6 mmol, 1.1 eq), and 50 mL of N,N-dimethylformamide (DMF). The reaction mixture was stirred overnight. Analysis by HPLC indicated the reaction was incomplete. Additional cesium carbonate (2.85 g) was added to the reaction mixture and the mixture was heated to 50° C. overnight. Analysis by HPLC indicated the reaction was complete and the reaction mixture was poured into a brine solution (250 g of sodium chloride in 800 mL of deionized water). After 20 minutes, a dark brown/black material precipitated and was filtered. The solid material was dissolved in chloroform, dried over magnesium sulfate, and purified by chromatography on a HORIZON HPFC system (eluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 30:70). The combined fractions were concentrated, dissolved in dichloromethane and methanol, and concentrated under reduced pressure to yield 1.18 g of 8-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine.

Workup

  1. customprepared
  2. waitAfter 20 minutes
  3. customa dark brown/black material precipitated
  4. filtrationwas filtered
  5. dissolutionThe solid material was dissolved in chloroform
  6. dry with materialdried over magnesium sulfate
  7. custompurified by chromatography on a HORIZON HPFC system (
  8. washeluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 30:70)
  9. concentrationThe combined fractions were concentrated
  10. dissolutiondissolved in dichloromethane
  11. concentrationmethanol, and concentrated under reduced pressure

Sources & evidence

ORD record
ord-3c3273068d2843b98837a8c8f9589404
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

Loading…