Triethylamine → 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromide

HRID 244811

Reaction equation

HRID 244811 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([CH2:16][CH2:17][CH2:18][O:19][CH:20]([CH3:22])[CH3:21])[C:14]([CH2:23][O:24][CH2:25][CH3:26])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.[CH:27]([S:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[CH2:28].C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C1(C)C=CC=CC=1>[BrH:1].[CH2:25]([O:24][CH2:23][C:14]1[N:15]([CH2:16][CH2:17][CH2:18][O:19][CH:20]([CH3:22])[CH3:21])[C:6]2[C:5]3[CH:4]=[CH:3][C:2](/[CH:28]=[CH:27]/[S:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:11][C:10]=3[N:9]=[C:8]([NH2:12])[C:7]=2[N:13]=1)[CH3:26]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 74572Phenyl Vinyl SulfideHCID 673820847-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine

Product 1

HCID 690786562-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromideYield 25.5%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine (1.00 g, 2.46 mmol), tris(2-tolyl)phosphine (16 mg, 0.05 mmol) and a stir bar were added to a pressure vessel. Palladium(II) acetate (6 mg, 0.025 mmol), phenyl vinyl sulfide (0.330 mL, 2.53 mmol) and triethylamine (0.685 mL, 4.92 mmol) were subsequently added, followed by toluene (5 mL). The vessel was sealed with a TEFLON cap and the reaction was heated at 110° C. for 40 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, eluting with a linear gradient of 1-7% methanol in dichloromethane), followed by recrystallization from acetonitrile to provide 0.35 g of 2-ethoxymethyl-1-(3-isopropoxypropyl)-7-[(E)-2-(phenylthio)ethenyl]-1H-imidazo[4,5-c]quinolin-4-amine hydrobromide as yellow-orange crystals, mp 220-221° C.

Workup

  1. customcap
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography (silica gel
  5. washeluting with a linear gradient of 1-7% methanol in dichloromethane),
  6. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-799a88f2eb5e4cb8b93c2d20c306a584
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Linked notes

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