1,2-Dichloroethane → 7-(3,5-dimethylisoxazol-4-yl)-N-ethyl-8-methoxy-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-c]quinolin-2-amine

HRID 81999Notes

Reaction equation

HRID 81999 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:16]=[C:15]3[C:10]([C:11]([NH:18][CH2:19][CH:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[C:12]([NH2:17])[CH:13]=[N:14]3)=[CH:9][C:8]=2[O:26][CH3:27])=[C:5]([CH3:28])[O:4][N:3]=1.[CH2:29]([N:31]=[C:32]=S)[CH3:30].C(Cl)CCl>CO.C1COCC1>[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:26][CH3:27])=[CH:9][C:10]3[C:11]4[N:18]([CH2:19][CH:20]5[CH2:21][CH2:22][O:23][CH2:24][CH2:25]5)[C:32]([NH:31][CH2:29][CH3:30])=[N:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:28])[O:4][N:3]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 10966Ethyl isothiocyanateHCID 709811557-(3,5-dimethylisoxazol-4-yl)-6-methoxy-N4-((tetrahydro-2H-pyran-4-yl)methyl)quinoline-3,4-diamine

Product 1

HCID 665712847-(3,5-dimethylisoxazol-4-yl)-N-ethyl-8-methoxy-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-c]quinolin-2-amineYield 32.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

7-(3,5-Dimethylisoxazol-4-yl)-6-methoxy-N4-((tetrahydro-2H-pyran-4-yl)methyl)quinoline-3,4-diamine (for a preparation see Intermediate 17) (100 mg, 0.261 mmol) was dissolved in methanol and ethyl isothiocyanate (45.6 mg, 0.523 mmol) was added. The mixture was heated at 50° C. for 6 h, cooled and evaporated in vacuo to give a beige solid residue. This was re-dissolved in THF (5 ml) and EDC (100 mg, 0.523 mmol) was added, then the mixture heated at 60° C. overnight. The solvent was evaporated in vacuo and the residue dissolved in DCM (10 ml) and washed with water (10 ml), the organic layer dried and evaporated and the residue dissolved in DCM (2 ml) and loaded onto a 10 g silica column, then eluted with 2M methanolic ammonia/DCM (0-10%) and product-containing fractions evaporated in vacuo to give 7-(3,5-dimethylisoxazol-4-yl)-N-ethyl-8-methoxy-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-imidazo[4,5-c]quinolin-2-amine (37 mg, 0.085 mmol, 32.5% yield) as a colourless glass. LCMS (formate) Rt 0.71 min, MH+ 436

Workup

  1. temperaturecooled
  2. customevaporated in vacuo
  3. customto give a beige solid residue
  4. temperaturethe mixture heated at 60° C. overnight
  5. customThe solvent was evaporated in vacuo
  6. dissolutionthe residue dissolved in DCM (10 ml)
  7. washwashed with water (10 ml)
  8. customthe organic layer dried
  9. customevaporated
  10. dissolutionthe residue dissolved in DCM (2 ml)
  11. washeluted with 2M methanolic ammonia/DCM (0-10%)
  12. additionproduct-containing fractions
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-8b55a960e9b94cd6a443b9ad9a8a863c
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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