Tetrahydrofuran → 1-{3-[4-amino-8-(2-aminoethyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one

HRID 244871Notes

Reaction equation

HRID 244871 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][CH2:25][O:26][CH3:27])[N:14]([CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][C:19]3=[O:23])[C:10]=2[C:9]2[CH:8]=[C:7]([CH2:28][CH2:29][N:30]3C(=O)C4C(=CC=CC=4)C3=O)[CH:6]=[CH:5][C:4]=2[N:3]=1.O1CCCC1.O.NN>C(O)C>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][CH2:25][O:26][CH3:27])[N:14]([CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][C:19]3=[O:23])[C:10]=2[C:9]2[CH:8]=[C:7]([CH2:28][CH2:29][NH2:30])[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 24654Hydrazine hydrate (1:1)2×HCID 690766432-(2-{4-amino-2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}ethyl)-1H-isoindole-1,3(2H)dione

Product 1

HCID 576572621-{3-[4-amino-8-(2-aminoethyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-oneYield 38.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-(2-{4-Amino-2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}ethyl)-1H-isoindole-1,3(2H)dione (2.2 g, 4.1 mmol) was dissolved in 2:1 ethanol:tetrahydrofuran (40 mL), combined with hydrazine hydrate (410 mg, 8.2 mmol) and heated at reflux temperature for three hours. Additional hydrazine hydrate (0.25 mL) was added and the solution was refluxed for an additional 1.5 hours. The reaction was cooled to ambient temperature, filtered and the filtrate concentrated under reduce pressure. Purification by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-40% CMA:chloroform gradient over 3.8 L) provided 650 mg of 1-{3-[4-amino-8-(2-aminoethyl)-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one as an off-white solid. MS (ESI) m/z 411 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for three hours
  3. temperaturethe solution was refluxed for an additional 1.5 hours
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated
  6. customPurification by chromatography
  7. washeluting with a 0-40% CMA

Sources & evidence

ORD record
ord-c764cff3d85940a1b48fac4dbf64836d
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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