Methanol → HCID 58833635, compound

HRID 540860Notes

Reaction equation

HRID 540860 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].CS(OS(C)(=O)=O)(=O)=O.[NH2:14][C:15]1[C:24]2[N:25]=[C:26]([CH2:37][CH2:38][CH3:39])[N:27]([CH2:28][CH2:29][CH2:30][CH2:31][NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:23]=2[C:22]2[CH:21]=[CH:20][C:19]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][NH2:47])=[CH:18][C:17]=2[N:16]=1.CO>ClCCl>[NH2:14][C:15]1[C:24]2[N:25]=[C:26]([CH2:37][CH2:38][CH3:39])[N:27]([CH2:28][CH2:29][CH2:30][CH2:31][NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:23]=2[C:22]2[CH:21]=[CH:20][C:19]([O:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][NH:47][C:1](=[O:3])[CH3:2])=[CH:18][C:17]=2[N:16]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6367Acetyl chlorideHCID 81560Methanesulfonic anhydrideHCID 68968681HCID 68968681, compound

Product 1

HCID 58833635HCID 58833635, compoundYield 33.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A modification of the method described in Park K of Example 45 was followed using acetyl chloride (135 μL, 1.91 mmol) in lieu of methanesulfonic anhydride and N-{4-[4-amino-7-(6-aminohexyloxy)-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl]butyl}methanesulfonamide (0.85 g, 1.7 mmol) as the starting material. The crude product was purified by column chromatography on silica gel (eluting sequentially with 90:10 and 80:20 dichloromethane:methanol). The resulting white powder was stirred with water, isolated by filtration, and dissolved in 50:50 dichloromethane:methanol. The solution was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was recrystallized from acetonitrile, and the crystals were dissolved in dichloromethane:methanol, concentrated under reduced pressure, and further dried overnight under high vacuum at 60° C. to provide 0.30 g of N-(6-{4-amino-1-[4-(methanesulfonylamino)butyl]-2-propyl-1H-imidazo[4,5-c]quinolin-7-yloxy}hexyl)acetamide as a white powder, mp 168-172° C.

Workup

  1. customThe crude product was purified by column chromatography on silica gel (
  2. washeluting sequentially with 90:10 and 80:20 dichloromethane
  3. customisolated by filtration
  4. dry with materialThe solution was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting solid was recrystallized from acetonitrile
  8. dissolutionthe crystals were dissolved in dichloromethane
  9. concentrationmethanol, concentrated under reduced pressure
  10. customfurther dried overnight under high vacuum at 60° C.

Sources & evidence

ORD record
ord-22d5c31f97624377b0b51011de12a534
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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