1-Hydroxybenzotriazole → HCID 68929484, compound

HRID 1845730Notes

Reaction equation

HRID 1845730 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].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:39]([O:41][CH2:42][C:43]1[N:44]([CH2:56][C:57]([NH2:60])([CH3:59])[CH3:58])[C:45]2[C:54]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[N:48]=[CH:47][C:46]=2[N:55]=1)[CH3:40]>CN(C=O)C>[CH2:39]([O:41][CH2:42][C:43]1[N:44]([CH2:56][C:57]([NH:60][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])([CH3:59])[CH3:58])[C:45]2[C:54]3[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=3[N:48]=[CH:47][C:46]=2[N:55]=1)[CH3:40]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 6376026-((tert-Butoxycarbonyl)amino)hexanoic acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 68924425HCID 68924425, compound

Product 1

HCID 68929484HCID 68929484, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-[(tert-Butoxycarbonyl)amino]hexanoic acid (6.81 g, 29.5 mmol), 1-hydroxybenzotriazole (3.98 g, 29.5 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (5.66 g, 29.5 mmol) were added to a 0° C. solution of 2-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethylamine (which was prepared by acid-mediated deprotection of tert-butyl 2-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethylcarbamate, which is described in U.S. Patent Publication No. 2004/0091491, 8.00 g, 26.8 mmol) in DMF (80 mL). The solution was stirred at room temperature overnight. More 6-[(tert-butoxycarbonyl)amino]hexanoic acid and EDC were added and the solution was stirred for an additional hour. The solution was partitioned between aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×). The organic layers were combined, washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to provide 3.99 g of tert-butyl 6-({2-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}amino)-6-oxohexylcarbamate as a foam.

Workup

  1. stirringthe solution was stirred for an additional hour
  2. customThe solution was partitioned between aqueous sodium bicarbonate and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-cf09062df1044ee6adfabc4064c69052
Source dataset
uspto-grants-2015_02
Patent number
US08951528B2

Reaction notes

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