4-(Chloromethyl)benzoyl chloride → N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamide

HRID 746496Notes

Reaction equation

HRID 746496 reaction equation
[Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[NH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[C:29]2[C:28]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N:22]=[C:21]([NH2:30])[C:20]=2[N:19]=[CH:18]1>ClCCl.N1C=CC=CC=1.C(Cl)(Cl)Cl.CO>[NH2:30][C:21]1[C:20]2[N:19]=[CH:18][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][NH:12][C:7](=[O:8])[C:6]3[CH:10]=[CH:11][C:3]([CH2:2][Cl:1])=[CH:4][CH:5]=3)[C:29]=2[C:28]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[N:22]=1

Participants

7

Reactant 2

HCID 701364-(Chloromethyl)benzoyl chlorideHCID 154537751-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 23512685N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamide

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(chloromethyl)benzoyl chloride (1.06 g, 5.6 mmol) in dichloromethane was added to a suspension of 1-(4-aminobutyl)-1H-imidazo[4,5-c]quinolin-4-amine (1.0 g, 3.9 mmol) in pyridine (250 mL). After 1 hour HPLC analysis indicated that the reaction was complete. The reaction mixture was concentrated under vacuum. The residue was combined with saturated aqueous sodium bicarbonate. A solid was isolated by filtration then dissolved in chloroform containing a small amount of methanol. The solution was washed with saturated aqueous sodium bicarbonate. The organic layer was concentrated under vacuum. The resulting residue was purified by column chromatography (silica gel eluting with 10% methanol in dichloromethane) to provide N1-[4-(4-amino-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-4-(chloromethyl)benzamide as a solid, m.p. 240-300 (dec.). 1H NMR (500 MHz, DMSO-d6) δ 8.49 (t, J=6.0 Hz, 1H), 8.21 (s, 1H), 8.03 (d, J=8.0 Hz, 1H);7.76 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.0 Hz, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.42 (t, J=8.0 Hz, 1H), 7.20 (t, J=8.0 Hz, 1H), 6.80 (broad s, 2H), 4.78 (s, 2H), 4.62 (t, J=7.0 Hz, 2H), 3.28 (q, J=6.0 Hz, 2H), 1.89 (quintet, J=7.0 Hz, 2H), 1.56 (quintet, J=7.0 Hz, 2H); MS (CI) m/e 408 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. customA solid was isolated by filtration
  3. washThe solution was washed with saturated aqueous sodium bicarbonate
  4. concentrationThe organic layer was concentrated under vacuum
  5. customThe resulting residue was purified by column chromatography (silica gel eluting with 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f8dac6347cce4c3a847712ab2cf6f540
Source dataset
uspto-grants-2008_07
Patent number
US07393859B2

Reaction notes

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