Methanol → N-(2-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethyl)-3-mercaptopropanamide

HRID 1845729Notes

Reaction equation

[NH2:1][CH2:2][CH2:3][O:4][N:5]1[C:17]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([NH2:18])[C:8]=2[N:7]=[C:6]1[CH2:19][O:20][CH2:21][CH3:22].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)[S:30][CH2:31][CH2:32][C:33](ON2C(=O)CCC2=O)=[O:34])C=CC=CC=1.CO>ClCCl>[NH2:18][C:9]1[C:8]2[N:7]=[C:6]([CH2:19][O:20][CH2:21][CH3:22])[N:5]([O:4][CH2:3][CH2:2][NH:1][C:33](=[O:34])[CH2:32][CH2:31][SH:30])[C:17]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 1-(2-aminoethoxy)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (30 mg, 0.10 mmol) and succinimido 3-(triphenylmethylthio)propanoate (54 mg, 0.12 mmol) in dichloromethane (1 mL) was stirred for 24 hours at room temperature. Methanol (1 mL) was added and stirring was continued for another 5 days. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in dichloromethane (2 mL) and triethylsilane (0.16 mL) and cooled to 0° C. Trifluoroacetic acid (0.4 mL) was added. The solution was stirred for 30 min; then it was concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (gradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform) to provide 18.2 mg of N-(2-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]oxy}ethyl)-3-mercaptopropanamide as a solid. HRMS (ESI) calcd for C18H24N5O3S+H 390.1600, found 390.1579.

Workup

filtrationThe mixture was filtered
concentrationthe filtrate was concentrated
dissolutionThe residue was dissolved in dichloromethane (2 mL)
additionTrifluoroacetic acid (0.4 mL) was added
stirringThe solution was stirred for 30 min
concentrationthen it was concentrated under reduced pressure
customThe crude product was purified by flash chromatography on silica gel (
washgradient elution with a solution of 2% ammonium hydroxide in methanol and chloroform)

Sources & evidence

ORD record: ord-72f9f92e5e62455bb08f7114b9d61087
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08951528B2

Reaction notes

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