2-(4-Benzoylphenoxy)acetic acid → N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-benzoylphenoxy)acetamide

HRID 353838Notes

Reaction equation

HRID 353838 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][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]=[CH:7]1.[C:20]([C:28]1[CH:38]=[CH:37][C:31]([O:32][CH2:33][C:34](O)=[O:35])=[CH:30][CH:29]=1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[NH2:19][C:10]1[C:9]2[N:8]=[CH:7][N:6]([CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:34](=[O:35])[CH2:33][O:32][C:31]3[CH:30]=[CH:29][C:28]([C:20](=[O:27])[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:38][CH:37]=3)[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:11]=1

Participants

5

Reactant 3

HCID 806092-(4-Benzoylphenoxy)acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 154537751-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 12144522N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-benzoylphenoxy)acetamideYield 36.4%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

1-(4-Aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (99.6 mg, 0.39 mmol) and 2-(4-benzoylphenoxy)acetic acid (100 mg, 0.39 mmol) were combined in pyridine (10 mL). The mixture was warmed until homogeneous and then allowed to cool. 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (82 mg, 0.43 mole) was added. The reaction mixture was maintained at ambient temperature overnight and then concentrated under vacuum. The residue was partitioned between chloroform and saturated potassium carbonate solution. The layers were separated. The aqueous layer was extracted with chloroform. The organic layers were combined, dried over magnesium sulfate and then concentrated under vacuum to provide a gold oil. The oil was purified by column chromatography (silica gel eluting with 10% methanol in dichloromethane) to provide about 70 mg of N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-(4-benzoylphenoxy)acetamide as a white solid, m.p. 73-98° C. 1H NMR (500 MHz, DMSO-d6) δ 8.22 (t, J=6.0 Hz, 1H), 8.18 (s, 1H), 8.03 (d, J=8.3 Hz, 1H), 7.73 (d, J=8.0 Hz, 2H), 7.68 (d, J=8.0 Hz, 2H), 7.65 (t, J=8.0 Hz, 1H), 7.60 (dd, J=8.0, 1.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 2H), 7.42 (dt, J=8.0, 1.0 Hz, 1H), 7.25 (t, J=8.0, 1.0 Hz, 1H), 7.07 (d, J=8.0 Hz, 2H), 6.58 (broad s, 2H), 4.61 (t, J=7.0 Hz, 2H), 4.56 (s, 2H), 3.18 (q, J=6.0 Hz, 2H), 1.86 (quintet, J=7.0 Hz, 2H), 1.50 (quintet, J=7.0 Hz, 2H); MS (EI) m/e 493.2106 (493.2114 calcd for C29H27N5O3).

Workup

  1. temperatureThe mixture was warmed until homogeneous and
  2. temperatureto cool
  3. concentrationconcentrated under vacuum
  4. customThe residue was partitioned between chloroform and saturated potassium carbonate solution
  5. customThe layers were separated
  6. extractionThe aqueous layer was extracted with chloroform
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. customto provide a gold oil
  10. customThe oil was purified by column chromatography (silica gel eluting with 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c1dacf83cbf944929ebae0b42fa407e6
Source dataset
uspto-grants-2004_06
Patent number
US06756382B2

Reaction notes

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