Triethylamine → HCID 11696679, compound

HRID 1373973Notes

Reaction equation

HRID 1373973 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][O:21][CH2:22][CH3:23].C(N(CC)CC)C.[C:31](Cl)(=[O:35])[CH:32]([CH3:34])[CH3:33]>C(Cl)Cl.C(Cl)(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[NH2:19][C:10]1[C:9]2[N:8]=[C:7]([CH2:20][O:21][CH2:22][CH3:23])[N:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][C:31](=[O:35])[CH:32]([CH3:34])[CH3:33])[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 86594228HCID 86594228, compound

Product 1

HCID 11696679HCID 11696679, compoundYield 67.2%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of N1-(3-aminopropyl)-2-ethoxymethyl-1H-imidazo[4,5-c]quinoline-1,4-diamine (1.00 g, 3.18 mmol) in 25 mL of CH2Cl2 was placed under an atmosphere of nitrogen and then chilled in an ice water bath. The solution was treated with triethylamine (0.89 mL, 6.7 mmol) and then slowly with isobutyryl chloride (0.35 mL, 3.3 mmol). The reaction was stirred and allowed to slowly come to ambient temperature. After 16 h, the reaction was diluted with 15 mL of CHCl3 and 15 mL of 10% Na2CO3 solution and the layers were separated. The organic portion was washed with H2O (15 mL). The combined aqueous washes were back-extracted with CHCl3 (10 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a light yellow foam. The foam was purified by chromatography (SiO2, 10–50% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3) to yield a white foam. The foam was triturated with hexanes and filtered to yield N-(3-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]amino}propyl)-2-methylpropanamide (0.821 g) as a white solid. mp 108–110° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.43 (d, J=7.5 Hz, 1H), 7.72 (t, J=5.4 Hz, 1H), 7.58 (d, J=7.9 Hz, 1H), 7.46–7.41 (m, 1H), 7.26–7.21 (m, 1H), 6.97 (t, J=5.5 Hz, 1H), 6.62 (s, 2H), 4.75 (s, 2H), 3.61 (q, J=7.0 Hz, 2H), 3.17–3.13 (m, 4H), 2.29 (h, J=6.9 Hz, 1H), 1.71 (p, J=7.1 Hz, 2H), 1.17 (t, J=7.0 Hz, 3H), 0.95 (d, J=6.8 Hz, 3H); 13C NMR (75 MHz, DMSO-d6) δ 176.4, 152.3, 149.5, 145.3, 132.4, 127.4, 126.1, 124.2, 121.2, 114.7, 65.8, 63.1, 50.2, 36.6, 34.4, 28.0, 19.9, 15.3; MS (APCI) m/z 385 (M+H)+; Anal. Calcd for C20H28N6O2•0.25H2O: C, 61.76; H, 7.38; N, 21.61; Found: C, 61.67; H, 7.55; N, 21.72.

Workup

  1. temperaturechilled in an ice water bath
  2. customto slowly come to ambient temperature
  3. customthe layers were separated
  4. washThe organic portion was washed with H2O (15 mL)
  5. extractionThe combined aqueous washes were back-extracted with CHCl3 (10 mL)
  6. washThe combined organic extracts were washed with brine (15 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto yield a light yellow foam
  11. customThe foam was purified by chromatography (SiO2, 10–50% (80:18:2 CHCl3:MeOH:NH4OH) in CHCl3)
  12. customto yield a white foam
  13. customThe foam was triturated with hexanes
  14. filtrationfiltered

Sources & evidence

ORD record
ord-fd1dad270083432fb1789fe54faa1d23
Source dataset
uspto-grants-2007_01
Patent number
US07163947B2

Reaction notes

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