Dimethylformamide → N-(2-{4-amino-2-(ethoxymethyl)-7-[(3-thien-2-ylprop-2-ynyl)oxy]-1H-imidazo[4,5-c]quinolin-1-yl}-1,1-dimethylethyl)methanesulfonamide

HRID 2383225Notes

Reaction equation

HRID 2383225 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][O:25][CH2:26][CH3:27])[N:14]([CH2:15][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:28][CH2:29][C:30]#[CH:31])=[CH:5][C:4]=2[N:3]=1.I[C:33]1[S:34][CH:35]=[CH:36][CH:37]=1.C(N(CC)CC)C.CN(C=O)C>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CO.O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:24][O:25][CH2:26][CH3:27])[N:14]([CH2:15][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])([CH3:17])[CH3:18])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:28][CH2:29][C:30]#[C:31][C:33]3[S:34][CH:35]=[CH:36][CH:37]=3)=[CH:5][C:4]=2[N:3]=1

Participants

10

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 189212-IodothiopheneHCID 86626178N-{2-[4-amino-2-(ethoxymethyl)-7-(prop-2-ynyloxy)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}methanesulfonamide

Product 1

HCID 67051119N-(2-{4-amino-2-(ethoxymethyl)-7-[(3-thien-2-ylprop-2-ynyl)oxy]-1H-imidazo[4,5-c]quinolin-1-yl}-1,1-dimethylethyl)methanesulfonamideYield 127.3%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

N-{2-[4-Amino-2-(ethoxymethyl)-7-(prop-2-ynyloxy)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}methanesulfonamide (600 mg, 1.34 mmol), 2-iodothiophene (565 mg, 2.69 mmol), triethylamine (0.50 mL, 3.5 mmol), dichlorobis(triphenylphosphine)palladium(II) (19 mg, 0.03 mmol), copper(I) iodide (10 mg, 0.05 mmol), and DMF (10 mL) were combined and heated at 60° C. overnight. After cooling to ambient temperature, the reaction was poured into water (200 mL) and a fine precipitate formed. After the mixture was stirred for 1 hour, the solid was isolated by filtration. The solid was dissolved in dichloromethane and methanol and was passed through a plug of silica gel, which was rinsed with 20% methanol in dichloromethane. The filtrate was concentrated under reduced pressure to yield approximately 900 mg of N-(2-{4-amino-2-(ethoxymethyl)-7-[(3-thien-2-ylprop-2-ynyl)oxy]-1H-imidazo[4,5-c]quinolin-1-yl}-1,1-dimethylethyl)methanesulfonamide as a dark brown semi-solid that was used without further purification in the next step.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customa fine precipitate formed
  3. customthe solid was isolated by filtration
  4. washwas rinsed with 20% methanol in dichloromethane
  5. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a7b6ec6fd7994f1c823a25c4e6fa8af0
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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