Phenyl isocyanate → N-{8-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]octyl}-N'-phenylurea

HRID 1837568Notes

Reaction equation

[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:22]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]=[C:14]([NH2:23])[C:13]=2[N:12]=[C:11]1[CH2:24][CH2:25][O:26][CH3:27].[C:28]1([N:34]=[C:35]=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl>[NH2:23][C:14]1[C:13]2[N:12]=[C:11]([CH2:24][CH2:25][O:26][CH3:27])[N:10]([CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][NH:1][C:35]([NH:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:36])[C:22]=2[C:21]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Under a nitrogen atmosphere a mixture of 1-(8-aminooctyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-4-amine (1.5 g, 4.06 mmol) and dichloromethane (50 mL) was cooled to 0° C. Phenyl isocyanate was added dropwise. The reaction mixture was allowed to slowly warm to ambient temperature overnight. The reaction mixture was concentrated under reduced pressure. The crude product was purified by column chromatography (110 g silica gel eluting with 9:1 dichloromethane:methanol). The resulting orange solid was triturated with hexanes, isolated by filtration and then dried. This material was recrystallized from propyl acetate with a small amount of methanol, isolated by filtration, washed with hexanes, and then dried in a vacuum oven at 60° C. for 2 days to provide 0.6 g of N-{8-[4-amino-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]octyl}-N′-phenylurea as an off white powder, m.p. 136-142° C. Analysis: Calculated for C28H36N6O2: %C, 68.83; %H, 7.43; %N, 17.20; Found: %C, 68.27; %H, 7.44; %N, 16.85.

Workup

temperatureto slowly warm to ambient temperature overnight
concentrationThe reaction mixture was concentrated under reduced pressure
customThe crude product was purified by column chromatography (110 g silica gel eluting with 9:1 dichloromethane:methanol)
customThe resulting orange solid was triturated with hexanes
customisolated by filtration
customdried
customThis material was recrystallized from propyl acetate with a small amount of methanol
customisolated by filtration
washwashed with hexanes
customdried in a vacuum oven at 60° C. for 2 days

Sources & evidence

ORD record: ord-3b74ee82a13246caae7cd4069e8798d1
Source dataset: uspto-grants-2004_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06784188B2

Reaction notes

Loading…