Nicotinic Acid → N-(2-(1-(4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yloxy)ethyl)nicotinamide

HRID 522827Notes

Reaction equation

HRID 522827 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:41][CH2:42][CH2:43][O:44][C:45]([CH3:66])([CH3:65])[CH2:46][N:47]1[C:59]2[C:58]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[N:52]=[C:51]([NH2:60])[C:50]=2[N:49]=[C:48]1[CH2:61][O:62][CH2:63][CH3:64]>CN(C=O)C>[NH2:60][C:51]1[C:50]2[N:49]=[C:48]([CH2:61][O:62][CH2:63][CH3:64])[N:47]([CH2:46][C:45]([CH3:66])([O:44][CH2:43][CH2:42][NH:41][C:1](=[O:9])[C:2]3[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=3)[CH3:65])[C:59]=2[C:58]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[N:52]=1

Participants

6

Reactant 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 1184515851-(2-(2-Aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 118451566N-(2-(1-(4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yloxy)ethyl)nicotinamideYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Nicotinic acid (11.4 mg, 92.3 μmol) was combined with DMF (1.0 mL) to give a colorless solution. To this solution was added TBTU (29.6 mg, 92.3 μmol), and DIEA (54.2 mg, 71.8 μl) were added. Finally 1-(2-(2-aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (30 mg, 83.9 μmol) was added and the reaction mixture was stirred for 1 hour at room temperature. Volatiles were removed in high vacuum at 40° C. The residue was dissolve in a mixture of ethyl acetate (5 mL) and methanol (0.5 mL). 1N sodium hydroxide solution (1.5 mL) was added and after a few minutes stirring the layers were separated. The aqueous layer was extracted with ethyl acetate. The organic phases were combined dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel-NH2, 0% to 10% methanol in DCM) to give the title product (33 mg, 85%) as white foam; LC-MS (UV peak area, ESI) 88%, 463.2459 (MH+).

Workup

  1. customto give a colorless solution
  2. additionwere added
  3. customVolatiles were removed in high vacuum at 40° C
  4. dissolutionThe residue was dissolve in a mixture of ethyl acetate (5 mL) and methanol (0.5 mL)
  5. addition1N sodium hydroxide solution (1.5 mL) was added and after a few minutes
  6. stirringstirring the layers
  7. customwere separated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialThe organic phases were combined dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography (silica gel-NH2, 0% to 10% methanol in DCM)

Sources & evidence

ORD record
ord-fd574c64b95f41d4a0a59c0664f1d97d
Source dataset
uspto-grants-2016_05
Patent number
US09334268B2

Reaction notes

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