Hydrochloric Acid → HCID 11515373, compound

HRID 1373983Notes

Reaction equation

HRID 1373983 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][N:6]1[C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[N:11]=[C:10]([NH2:19])[C:9]=2[N:8]=[C:7]1[CH2:20][CH3:21].C(N(CC)CC)C.[C:29](Cl)(=[O:31])[CH3:30].Cl>C(Cl)Cl.CO>[NH2:19][C:10]1[C:9]2[N:8]=[C:7]([CH2:20][CH3:21])[N:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][C:29](=[O:31])[CH3:30])[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6367Acetyl chloride2×HCID 8471TriethylamineHCID 86035857HCID 86035857, compound

Product 1

HCID 11515373HCID 11515373, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of N1-(3-Aminopropyl)-2-ethyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (0.89 g, 3.1 mmol) in 30 mL of CH2Cl2 was placed under an atmosphere of nitrogen. The solution was treated first with triethylamine (0.92 mL, 6.6 mmol) and then slowly with acetyl chloride (0.234 mL, 3.29 mmol). After 16 h, another equivalent of acetyl chloride was added. After 3 h, the reaction was concentrated under reduced pressure to yield an orange oil. The oil was then treated with 20 mL of 1 M HCl in MeOH and stirred at ambient temperature to hydrolyze any bis-amide. After 16 h, the reaction was quenched with 25 mL of 10% Na2CO3 solution. The mixture was concentrated under reduced pressure to remove MeOH. The aqueous oily suspension was treated with 75 mL of 95:5 CHCl3:MeOH, transferred to a separatory funnel and separated. The organic portion was washed with brine (25 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a yellow foam. The foam was purified by chromatography (40 g SiO2, 25% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3) to yield a light yellow solid. The solid was recrystallized from MeCN to give N-{3-[(4-amino-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)amino]propyl}acetamide (0.67 g) as yellow crystals. mp 167–169° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.42 (d, J=8.1 Hz, 1H), 7.85 (t, J=5.2 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.44–7.38 (m, 1H), 7.25–7.20 (m, 1H), 6.96 (t, J=5.3 Hz, 1H), 6.51 (s, 2H), 3.19–3.08 (m, 4H), 2.97 (q, J=7.4 Hz, 2H), 1.78 (s, 3H), 1.69 (p, J=7.0 Hz, 2H), 1.38 (t, J=7.5 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) δ 169.5, 154.9, 152.0, 144.9, 132.1, 126.9, 126.1, 124.2, 121.1, 121.0, 114.9, 49.7, 36.8, 28.0, 23.0, 19.5, 12.4; MS (ESI) m/z 327 (M+H)+; Anal. Calcd for C17H22N6O: C, 62.56; H, 6.79; N, 25.75; Found: C, 62.40; H, 7.06; N, 25.82.

Workup

  1. waitAfter 3 h
  2. concentrationthe reaction was concentrated under reduced pressure
  3. customto yield an orange oil
  4. waitAfter 16 h
  5. customthe reaction was quenched with 25 mL of 10% Na2CO3 solution
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customto remove MeOH
  8. additionThe aqueous oily suspension was treated with 75 mL of 95:5 CHCl3
  9. customMeOH, transferred to a separatory funnel
  10. customseparated
  11. washThe organic portion was washed with brine (25 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customto yield a yellow foam
  16. customThe foam was purified by chromatography (40 g SiO2, 25% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3)
  17. customto yield a light yellow solid
  18. customThe solid was recrystallized from MeCN

Sources & evidence

ORD record
ord-efedf6d170174a84badb430373e96bcf
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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