Hydrochloric Acid → HCID 57515406, compound

HRID 44730Notes

Reaction equation

HRID 44730 reaction equation
Cl.[NH2:2][C:3]1[C:12]2[N:13]=[C:14]([CH2:37][O:38][CH2:39][CH3:40])[N:15]([CH2:16][C:17]3([O:30][CH2:31][CH2:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1>C(O)C>[CH2:39]([O:38][CH2:37][C:14]1[N:15]([CH2:16][C:17]2([O:30][CH2:31][CH2:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[C:3]([NH2:2])[C:12]=2[N:13]=1)[CH3:40]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57515410HCID 57515410, compound

Product 1

HCID 57515406HCID 57515406, compoundYield 76.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of HCl in ethanol (4.2 M, 0.8 mL, 3.56 mmol) was added to a suspension of tert-butyl 4-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-4-[2-(methylsulfonyl)ethoxy]piperidine-1-carboxylate (0.40 g, 0.71 mmol) in ethanol (4 mL) at rt. The resulting yellow solution was heated at reflux for 1.5 h. The reaction was stirred at rt for 16 h, then was concentrated under reduced pressure. The resulting solid was dissolved in water (20 mL) and 20% aqueous NaOH was added until the pH=13. The solution was extracted with dichloromethane (3×50 mL). The organic layers were combined, washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to provide a solid that was crystallized from acetonitrile. The crystals were dried under vacuum at 65° C. to provide 2-(ethoxymethyl)-1-({4-[2-(methylsulfonyl)ethoxy]piperidin-4-yl}methyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.25 g, 76%) as crystalline plates, mp 212-214° C. 1H NMR (300 MHz, DMSO-d6) δ 8.26 (d, J=8.1 Hz, 1H), 7.61 (d, J=8.1 Hz, 1H), 7.44 (t, J=8.1 Hz, 1H), 7.26 (t, J=8.1 Hz, 1H), 6.61 (bs, 2H), 4.85 (s, 2H), 4.81 (s, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.55 (q, J=7.5 Hz, 2H), 3.19 (t, J=5.6 Hz, 2H), 2.92 (s, 3H) 2.66-2.58 (m, 4H), 1.84 (bs, 1H), 1.70-1.66 (m, 2H), 1.48-1.38 (m, 2H), 1.16 (t, J=7.5 Hz, 3H); MS (APCI) m/z 462 (M+H)+; Anal. Calcd for C22H31N5O4S: C, 57.25; H, 6.77: N, 15.17. Found: C, 57.48; H, 7.05; N, 15.57.

Workup

  1. temperatureThe resulting yellow solution was heated
  2. temperatureat reflux for 1.5 h
  3. concentrationwas concentrated under reduced pressure
  4. dissolutionThe resulting solid was dissolved in water (20 mL)
  5. addition20% aqueous NaOH was added until the pH=13
  6. extractionThe solution was extracted with dichloromethane (3×50 mL)
  7. washwashed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto provide a solid
  12. customthat was crystallized from acetonitrile
  13. customThe crystals were dried under vacuum at 65° C.

Sources & evidence

ORD record
ord-b5833a246cd74040bea659dd0f87f0a7
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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