Triethylamine → HCID 21984182, compound

HRID 244886Notes

Reaction equation

HRID 244886 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.[CH:25]([B-](F)(F)F)=[CH2:26].[K+].C(N(CC)CC)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(O)CC>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:19])([OH:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH:25]=[CH2:26])=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 219842117-bromo-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amineHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 21984182HCID 21984182, compoundYield 30.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 10311-PropanolSolvent

Conditions

Temperature
80 °C

Procedure

A round bottom flask, equipped with a stir bar, was charged with 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol (1.18 g, 3.0 mmol), 1-propanol (30 mL), potassium vinyltrifluoroborate (0.4 g, 3.0 mmol), triethylamine (1.25 mL, 9.0 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (Pd(dppf)), (11 mg, 0.015 mmol). The reaction mixture was heated at 80° C. for 66 hours. The reaction mixture was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The solid was dissolved in dichloromethane (100 mL) and washed with saturated aqueous potassium carbonate (50 mL). The fractions were separated and the organic fraction was concentrated to dryness. The off-white solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-15% CMA/chloroform). Recrystallization from acetonitrile provided 0.31 g of 1-[4-amino-2-(ethoxymethyl)-7-vinyl-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an off-white crystalline solid. MS (APCI) m/z 341 (M+H)+.

Workup

  1. customA round bottom flask, equipped with a stir bar
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. concentrationconcentrated to dryness under reduced pressure
  4. dissolutionThe solid was dissolved in dichloromethane (100 mL)
  5. washwashed with saturated aqueous potassium carbonate (50 mL)
  6. customThe fractions were separated
  7. concentrationthe organic fraction was concentrated to dryness
  8. customThe off-white solid was purified by chromatography
  9. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-c2cbcde8f6534e1398765d85bb760c46
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

Loading…