6-(((Phenylmethoxy)carbonyl)amino)hexanoic acid → HCID 68926476, compound

HRID 1845713Notes

Reaction equation

HRID 1845713 reaction equation
[C:1]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].ON1C(=O)CCC1=O.Cl.CN(C)CCCN=C=NCC.[NH2:40][C:41]([CH3:62])([CH3:61])[CH2:42][N:43]1[C:55]2[C:54]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[N:48]=[C:47]([NH2:56])[C:46]=2[N:45]=[C:44]1[CH2:57][O:58][CH2:59][CH3:60]>CN(C=O)C.O>[NH2:56][C:47]1[C:46]2[N:45]=[C:44]([CH2:57][O:58][CH2:59][CH3:60])[N:43]([CH2:42][C:41]([NH:40][C:17](=[O:19])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:1](=[O:2])[O:3][CH2:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=3)([CH3:61])[CH3:62])[C:55]=2[C:54]2[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=2[N:48]=1

Participants

7

Reactant 4

HCID 747586-(((Phenylmethoxy)carbonyl)amino)hexanoic acidHCID 80170N-HydroxysuccinimideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10380870TLR7/8 agonist 3

Product 1

HCID 68926476HCID 68926476, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 6-(carbobenzyloxyamino) caproic acid (8.49 grams (g), 32.0 millimole (mmol)) in DMF (50 mL) at 0° C. was added N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC). After a short period, the solution was added to a 0° C. solution of 1-(2-amino-2-methylpropyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine (prepared as described in U.S. Patent Publication No. 2004/0091491, 10 g, 32 mmol) in DMF (100 mL). The mixture was allowed to warm to room temperature and was stirred for 3 days. The solution was diluted with water (400 mL) and extracted with ethyl acetate (3×). The organic layers were combined and washed with water (2×) and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by HPFC on silica gel three times (gradient elution with CMA in chloroform) to provide 4.90 g of benzyl 6-({2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}amino)-6-oxohexylcarbamate as a white foam.

Workup

  1. waitAfter a short period
  2. extractionextracted with ethyl acetate (3×)
  3. washwashed with water (2×) and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by HPFC on silica gel three times (gradient elution with CMA in chloroform)

Sources & evidence

ORD record
ord-6d43b9e16897451090f2494f2956888e
Source dataset
uspto-grants-2015_02
Patent number
US08951528B2

Reaction notes

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