Triethylamine → 1-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol

HRID 598358Notes

Reaction equation

HRID 598358 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]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:24])=[CH:5][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:31]1[S:35][CH:34]=[N:33][C:32]=1[CH2:36]Cl.Cl.C(N(CC)CC)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[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]([CH3:18])([OH:19])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:36][C:32]3[N:33]=[CH:34][S:35][CH:31]=3)=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 27632894-(Chloromethyl)-1,3-thiazole hydrochlorideHCID 1363405384-amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol

Product 1

HCID 575453141-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-olYield 48.3%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Procedure

4-Amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol (100 mg, 0.3 mmol), cesium carbonate (488 mg, 1.5 mmol), 4-(chloromethyl)thiazoleHCl (102 mg, 0.6 mmol), tetrabutylammonium bromide (96 mg, 0.3 mmol), triethylamine (0.5 ml), and DMF (10 mL) were combined and stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure and dichloromethane was added to the residue. Undissolved solids were removed by filtration. The filtrate was concentrated under reduced pressure and subsequently purified by flash column chromatography on silica gel, eluting with a gradient of 0-4% methanol in dichloromethane. The clean fractions were combined and concentrated under reduced pressure. The resulting solid was recrystallized from acetonitrile to yield 62 mg of 1-[4-amino-2-ethoxymethyl-7-(thiazol-4-ylmethoxy)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white powder, mp 190.0-191.0° C.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure and dichloromethane
  2. additionwas added to the residue
  3. customwere removed by filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customsubsequently purified by flash column chromatography on silica gel
  6. washeluting with a gradient of 0-4% methanol in dichloromethane
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-c9990d687dfd489d8804312c99bb96af
Source dataset
uspto-grants-2011_03
Patent number
US07897597B2

Reaction notes

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