Diisopropylethylamine → tert-Butyl 6-(2-(1-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yloxy)ethylamino)-6-oxohexylcarbamate

HRID 63699

Reaction equation

HRID 63699 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:48][CH2:49][CH2:50][O:51][C:52]([CH3:73])([CH3:72])[CH2:53][N:54]1[C:66]2[C:65]3[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=3[N:59]=[C:58]([NH2:67])[C:57]=2[N:56]=[C:55]1[CH2:68][O:69][CH2:70][CH3:71]>CN(C=O)C>[NH2:67][C:58]1[C:57]2[N:56]=[C:55]([CH2:68][O:69][CH2:70][CH3:71])[N:54]([CH2:53][C:52]([CH3:73])([O:51][CH2:50][CH2:49][NH:48][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:72])[C:66]=2[C:65]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[N:59]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6376026-((tert-Butoxycarbonyl)amino)hexanoic acidHCID 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 118451670tert-Butyl 6-(2-(1-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-yloxy)ethylamino)-6-oxohexylcarbamateYield 27.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(tert-Butoxycarbonylamino)hexanoic acid (197 mg, 850 μmol) was combined with DMF (10.9 mL) to give a colorless solution. O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU, 300 mg, 936 μmol) and N,N-diisopropylethylamine (DIEA, 728 μl, 4.25 mmol) were added with stirring in an inert atmosphere. Then 1-(2-(2-aminoethoxy)-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (Example 1c, 304 mg, 850 μmol) was added and the mixture was stirred for 2 hours at room temperature. The mixture was concentrated in vacuo, dissolved in ethyl acetate (5 mL), stirred for 1 min with cold sodium hydroxide solution (1 N) and dried by passing through ChemElut® (10 g). The organic phase was concentrated in vacuo again and the residue was purified by flash chromatography (silica gel, 10% methanol in dichloromethane) to give the title compound (0.135 g, 23%) as light brown oil; LC-MS (UV peak area, ESI) 83%, 571.5 (MH+).

Workup

  1. customto give a colorless solution
  2. stirringthe mixture was stirred for 2 hours at room temperature
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutiondissolved in ethyl acetate (5 mL)
  5. stirringstirred for 1 min with cold sodium hydroxide solution (1 N)
  6. customdried
  7. concentrationThe organic phase was concentrated in vacuo again
  8. customthe residue was purified by flash chromatography (silica gel, 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-96897bc44d894967969b40444e977dcf
Source dataset
uspto-grants-2016_09
Patent number
US09447097B2

Linked notes

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