Dichloromethane → N2-{4-[4-amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide

HRID 353875

Reaction equation

HRID 353875 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11](Cl)=[O:12].[NH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]1[C:31]2[C:30]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N:24]=[C:23]([NH2:32])[C:22]=2[N:21]=[C:20]1[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1.ClCCl>C(N(CC)CC)C>[NH2:32][C:23]1[C:22]2[N:21]=[C:20]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[N:19]([CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[N:1]=3)=[O:12])[C:31]=2[C:30]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N:24]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 2760547Quinaldoyl chlorideHCID 22180874HCID 22180874, compound

Product 1

HCID 9936826N2-{4-[4-amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamideYield 27.5%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Quinoline-2-carbonyl chloride (0.28 g in 10 ml dichloromethane, 1.46 mmol) was added dropwise to a stirring solution of 1-(4-aminobutyl)-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.49 g, 1.3 mmol), dichloromethane (140 ml) and triethylamine (0.5 ml). The reaction was maintained for 17 hours and then concentrated in vacuo. The yellow residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic fraction was dried (MgSO4), filtered, and concentrated. The crude residue was purified by flash column chromatography (silica gel, gradient elution using dichloromethane to 95:5 dichloromethane\methanol) to provide 0.19 g of N2-{4-[4-amino-2-(4-methoxybenzyl)-1H-imidazo[4,5-c]quinolin-1-yl]butyl}-2-quinolinecarboxamide as an off white solid, m.p. 95.1-97.4° C. 1H NMR (300 MHz, DMSO-d6) δ 8.97 (t, J=6.0 Hz, 1H), 8.56 (d, J=8.4 Hz, 1H), 8.16-8.07 (m, 3H), 7.96 (d, J=7.7 Hz, 1H), 7.87 (m, 1H), 7.72 (m, 1H), 7.58 (dd, J=8.3, 1.1 Hz, 1H), 7.31 (m, 1H), 7.23 (d, J=8.7 Hz, 2H), 7.08 (m, 1H), 6.82 (d, J=8.7 Hz, 2H), 6.58 (broad s, 2H), 4.50 (m, 2H), 4.33 (s, 2H), 3.63 (s, 3H), 3.34 (m, 2H), 1.65 (m, 4H); MS (EI) m/e 530.2431 (530.2430 calcd for C32H30N6O2).

Workup

  1. temperatureThe reaction was maintained for 17 hours
  2. concentrationconcentrated in vacuo
  3. customThe yellow residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  4. dry with materialThe organic fraction was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash column chromatography (silica gel, gradient elution using dichloromethane to 95:5 dichloromethane\methanol)

Sources & evidence

ORD record
ord-f011b4837aa34b6fbb84edc83de03814
Source dataset
uspto-grants-2004_06
Patent number
US06756382B2

Linked notes

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