Triethylamine → n-[2-(4-Amino-2-(ethoxymethyl)-1h-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide

HRID 353846

Reaction equation

HRID 353846 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[C:16]([NH2:25])[C:15]=2[N:14]=[C:13]1[CH2:26][O:27][CH2:28][CH3:29].O[N:31]1[C:52](=[O:53])[NH:51][C@H:50]2[C@@H:32]1[CH2:33][S:34][C@H:35]2[CH2:36][CH2:37][CH2:38][CH:39](N1C(=O)CCC1=O)[C:40](=O)[OH:41]>C(Cl)(Cl)Cl>[NH2:25][C:16]1[C:15]2[N:14]=[C:13]([CH2:26][O:27][CH2:28][CH3:29])[N:12]([CH2:11][CH2:10][NH:9][C:40](=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]3[CH:50]4[CH:32]([NH:31][C:52](=[O:53])[NH:51]4)[CH2:33][S:34]3)[C:24]=2[C:23]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 224789881-(2-aminoethyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine hydrochlorideHCID 129676281N-Hydroxysuccinimido-d-biotin

Product 1

HCID 23512690n-[2-(4-Amino-2-(ethoxymethyl)-1h-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamideYield 13.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Triethylamine (1.2 g, 11.4 mmol) was added in a single portion to a slurry of 1-(2-aminoethyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine hydrochloride (3.39 g, 10.53 mmol) in chloroform (150 mL). The reaction mixture became clear. N-hydroxysuccinimidobiotin (3.0 g, 8.79 mmol) was then slowly added. After 2 hours the turbid reaction mixture was heated to reflux. The reaction mixture was maintained at reflux overnight and became clear. The reaction mixture was allowed to cool to ambient temperature and then it was quenched with water. The layers were separated. The organic layer was dried over magnesium sulfate and then concentrated to provide an off-white solid. This material was recrystallized from 8:2 ethanol:water to provide a white solid. A portion of this material was purified by prep HPLC eluting with water/acetonitrile/trifluoroacetic acid to provide 0.6 g of N1-[2-(4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-5-(2-oxoperhydrothieno[3,4-d]imidazol-4-yl)pentanamide as the ditrifluoroacetate salt, m.p. 171-175° C. Analysis: Calculated for: C25H33N7O3S.2 C2HF3O2: % C, 47.09; % H, 4.77; % N, 13.26. Found: % C, 47.06; % H, 5.17; % N, 13.31.

Workup

  1. customAfter 2 hours the turbid reaction mixture
  2. temperaturewas heated to reflux
  3. temperatureThe reaction mixture was maintained
  4. temperatureat reflux overnight
  5. customit was quenched with water
  6. customThe layers were separated
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated
  9. customto provide an off-white solid
  10. customThis material was recrystallized from 8:2 ethanol
  11. customwater to provide a white solid
  12. customA portion of this material was purified by prep HPLC
  13. washeluting with water/acetonitrile/trifluoroacetic acid

Sources & evidence

ORD record
ord-e60d1c2158764ec3b9c89e1f1e969b87
Source dataset
uspto-grants-2004_06
Patent number
US06756382B2

Linked notes

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