3-(Methylthio)-1-propanol → HCID 68971106, compound

HRID 2203570Notes

Reaction equation

HRID 2203570 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([OH:17])=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1.C(OC1C=C(C=CC=1)N)C1C=CC=CC=1.COCCC(Cl)=O.C(OC1C=CC(N)=CC=1)C1C=CC=CC=1.C(OCC(Cl)=O)C.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:99][S:100][CH2:101][CH2:102][CH2:103]O>O1CCCC1>[CH3:1][O:2][CH2:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[CH:14][C:13]([O:17][CH2:103][CH2:102][CH2:101][S:100][CH3:99])=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1

Participants

10

Reactant 8

HCID 104483-(Methylthio)-1-propanolHCID 11776TriphenylphosphineHCID 228604-BenzyloxyanilineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 84189Ethoxyacetyl chlorideHCID 928923-BenzyloxyanilineHCID 27597283-Methoxypropanoyl chlorideHCID 136347851HCID 136347851, compound2×

Product 1

HCID 68971106HCID 68971106, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A modification on the methods described in Parts A-H of Example 2 were used to prepare 2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol, with 3-benzyloxyaniline and 3-methoxypropanoyl chloride used in lieu of 4-benzyloxyaniline and ethoxyacetyl chloride, respectively. Diisopropyl azodicarboxylate (2.07 mL, 10.5 mmol) was added dropwise to a slurry of 2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol (2.00 g, 7.01 mmol), triphenylphosphine (2.75 g, 10.5 mmol), and 3-(methylthio)propan-1-ol (1.08 mL, 10.5 mmol) in tetrahydrofuran (70 mL) at 0° C. The solution was stirred for 30 minutes at 0° C., then at room temperature for 16 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate, treated with 1 M hydrochloric acid (40 mL), and stirred for 30 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The aqueous layer was adjusted to approximately pH 14 with 50% aqueous sodium hydroxide and then was extracted with dichloromethane (3×50 mL). The organic layers were combined, washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution with 1-4% methanol in dichloromethane) to provide 2.0 g of 2-(2-methoxyethyl)-7-[3-(methylthio)propoxy]-1-propyl-1H-imidazo[4,5-c]quinoline as an opaque solid.

Workup

  1. waitat room temperature for 16 hours
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. additiontreated with 1 M hydrochloric acid (40 mL)
  5. stirringstirred for 30 minutes
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×25 mL)
  8. extractionwas extracted with dichloromethane (3×50 mL)
  9. washwashed with water and saturated aqueous sodium chloride
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product was purified by flash chromatography (silica gel, gradient elution with 1-4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-3de7fda8c59e4f84a195177e8e92c4cc
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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