Morpholine → HCID 57657229, compound

HRID 244848Notes

Reaction equation

HRID 244848 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH3:22])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([OH:27])=O)=[CH:5][C:4]=2[N:3]=1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>N1C=CC=CC=1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH3:22])[N:14]([CH2:15][C:16]([CH3:18])([OH:19])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:23][CH2:24][C:25]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:27])=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 69080290HCID 69080290, compound

Product 1

HCID 57657229HCID 57657229, compoundYield 62.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

3-[4-Amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]propanoic acid (1.25 g, 3.30 mmol), anhydrous pyridine (75 mL) and 1-hydroxybenzotriazole (892 mg, 6.60 mmol) were combined and the reaction was stirred for 30 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (1.27 g, 6.60 mmol) was added and the reaction mixture was stirred for an additional 15 minutes. Morpholine (581 mg, 6.60 mmol) was added in one portion. After stirring for 18 hours the solution was concentrated under reduced pressure. The resulting foam was dissolved in chloroform (50 mL) and washed with 1% aqueous sodium carbonate (2×15 mL). The combined aqueous washes were extracted with chloroform. The combined organic fractions were concentrated under reduced pressure and then purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-20% CMA over 1500 mL, followed by 20-25% CMA over 500 mL, and finally 25-30% CMA over 500 mL). A final recrystallization from acetonitrile provided 913 mg of 3-[4-amino-2-(methoxymethyl)-7-(3-morpholin-4-yl-3-oxopropyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an off-white solid, mp 215-217° C.

Workup

  1. stirringthe reaction mixture was stirred for an additional 15 minutes
  2. stirringAfter stirring for 18 hours the solution
  3. concentrationwas concentrated under reduced pressure
  4. dissolutionThe resulting foam was dissolved in chloroform (50 mL)
  5. washwashed with 1% aqueous sodium carbonate (2×15 mL)
  6. extractionThe combined aqueous washes were extracted with chloroform
  7. concentrationThe combined organic fractions were concentrated under reduced pressure
  8. custompurified by chromatography
  9. washeluting with a CMA
  10. customA final recrystallization from acetonitrile

Sources & evidence

ORD record
ord-ff45d9b70d0d40f6830a9677b5fc91d0
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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