1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57657244, compound

HRID 244849Notes

Reaction equation

HRID 244849 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](O)=[O:26])=[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][S:52](=[O:56])(=[O:55])[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]([CH3:17])([OH:19])[CH3:18])[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][S:52](=[O:56])(=[O:55])[CH2:51][CH2:50]3)=[O:26])=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6484228Thiomorpholine 1,1-dioxideHCID 69080290HCID 69080290, compound

Product 1

HCID 57657244HCID 57657244, compoundYield 66.2%

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. Thiomorpholine 1,1-dioxide (895 mg, 6.60 mmol) was added in one portion. After stirring for 18 hours the solution was concentrated under reduced pressure and the residual foam was dissolved in chloroform (50 mL) and washed with 1% aqueous sodium carbonate (2×25 mL). The combined aqueous washes were extracted with chloroform. The combined organic fractions were concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-25% CMA over 1500 mL, followed by 25-30% CMA over 500 mL, finally 30% CMA over 1000 mL). The resulting material was subjected to a second chromatography purification using a HORIZON HPFC system (silica cartridge, eluting with CMA:chloroform gradient; 0-25% CMA over 1500 mL, followed by 25-30% CMA over 500 mL) followed by recrystallization from acetonitrile to provide 1.07 g of 1-[4-amino-7-[3-(1,1-dioxidothiomorpholin-4-yl)-3-oxopropyl]-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as a white solid, mp 190-192° 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 residual foam was dissolved in chloroform (50 mL)
  5. washwashed with 1% aqueous sodium carbonate (2×25 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. customThe resulting material was subjected to a second chromatography purification
  11. washa HORIZON HPFC system (silica cartridge, eluting with CMA:chloroform gradient; 0-25% CMA over 1500 mL, followed by 25-30% CMA over 500 mL)
  12. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-759b45515a30405aa59d42f841eec37b
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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