Cinchophen → N4-[4-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamide

HRID 746550

Reaction equation

HRID 746550 reaction equation
Cl.CN(C)CCCN=C=NCC.[C:13]1([C:19]2[CH:28]=[C:27]([C:29](O)=[O:30])[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ON1C2C=CC=CC=2N=N1.[NH2:42][CH2:43][CH2:44][CH2:45][CH2:46][N:47]1[C:59]2[C:58]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[N:52]=[C:51]([NH2:60])[C:50]=2[N:49]=[C:48]1[CH2:61][CH2:62][O:63][CH3:64]>ClCCl.N1C=CC=CC=1>[NH2:60][C:51]1[C:50]2[N:49]=[C:48]([CH2:61][CH2:62][O:63][CH3:64])[N:47]([CH2:46][CH2:45][CH2:44][CH2:43][NH:42][C:29]([C:27]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=[C:19]([C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:28]=3)=[O:30])[C:59]=2[C:58]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[N:52]=1

Participants

7

Reactant 4

HCID 8593CinchophenHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 221808721-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 12144531N4-[4-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamideYield 44.6%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.57 g, 3.0 mmol) was added dropwise to a chilled (0° C.) solution of 2-phenyl-4-quinolinecarboxylic acid (0.5 g, 3.7 mmol), 1-hydroxybenzotriazole (0.5 g, 3.7 mmol), pyridine (2.2 ml), and dichloromethane (20 ml). The reaction was maintained for 15 min followed by the dropwise addition of 1-(4-aminobutyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.8 g, 2.55 mmol) in dichloromethane (100 ml). The reaction was maintained at room temperature overnight. The solvent was removed in vacuo and the residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane\methanol). The fractions containing product were combined, washed with saturated aqueous sodium bicarbonate, dried (MgSO4), filtered, and concentrated to provide 0.62 g of N4-[4-(4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-2-phenyl-4-quinolinecarboxamide as a yellow crystalline solid, m.p. 118° C. (decomposition). 1H NMR (300 MHz, DMSO-d6) δ 8.88 (t, J=5.7 Hz, 1H), 8.24-8.21 (m, 2H), 8.13-8.01(m, 4H), 7.83-7.78 (m, 1H), 7.62-7.48 (m, 5H), 7.36 (m, 1H), 7.20 (dt, J=7.6, 1.2 Hz, 1H), 6.54 (broad s, 2H), 4.62 (t, J=7.2 Hz, 2H), 3.83 (t, J=6.7 Hz, 2H), 3.45 (m, 2H), 3.29-3.20 (m, 5H), 1.96 (m, 2H), 1.79 (m, 2H); MS (EI) m/e 544.2589 (544.2587 calcd for C33H32N6O2).

Workup

  1. temperatureThe reaction was maintained for 15 min
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by flash column chromatography (silica gel, 9:1 dichloromethane\methanol)
  4. additionThe fractions containing product
  5. washwashed with saturated aqueous sodium bicarbonate
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-4761f97b8728482983c3ed752ab8b189
Source dataset
uspto-grants-2008_07
Patent number
US07393859B2

Linked notes

Loading…