Pyridine → 3-[bis(methylthio)methylene]-1-(cyclobutylamino)quinoline-2,4(1H,3H)-dione

HRID 1444674Notes

Reaction equation

HRID 1444674 reaction equation
[CH:1]1([NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[CH:8][C:7]2=[O:17])[CH2:4][CH2:3][CH2:2]1.S(OC)(O[C:22](SC)([S:25][CH3:26])[S:23][CH3:24])(=O)=O.N1C=CC=CC=1>O1CCOCC1>[CH3:24][S:23][C:22]([S:25][CH3:26])=[C:8]1[C:9](=[O:16])[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:6]([NH:5][CH:1]2[CH2:2][CH2:3][CH2:4]2)[C:7]1=[O:17]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24976308Tris(methylthio)methyl methyl sulfate2×HCID 591688031-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 100882703-[bis(methylthio)methylene]-1-(cyclobutylamino)quinoline-2,4(1H,3H)-dioneYield 87%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 1-(cyclobutylamino)-4-hydroxyquinolin-2(1H)-one (0.115 g, 0.5 mmol) and tris(methylthio)methyl methyl sulfate (prepared using the procedures in SYNTHESIS, 22-25, 1988; M Barbero, S. Cadamuro, 1 Degani, R. Fochi, A. Gatti, V. Regondi) (0.27 g, 1.0 mmol) in pyridine (0.316 g, 4.0 mmol) and dioxane (5.0 mL) was heated at 60° C. for 30 minutes. Additional tris(methylthio)methyl methyl sulfate was added (0.27 g, 1.0 mmol) and heating continued for 30 minutes. The mixture was cooled to 25° C. and partitioned between ethyl acetate and water. The ethyl acetate layer was washed with water, brine, dried over sodium sulfate, filtered and concentrated. The crude material was chromatographed on silica gel eluting with 95/5 dichloromethane/ethyl acetate to give 3-[bis(methylthio)methylene]-1-(cyclobutylamino)quinoline-2,4(1H, 3H)-dione (0.146 g, 87% yield). MS (ESI+) m/z 335 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 1.54 (m, 1H) 1.66 (m, 1H) 1.99 (m, 4H) 2.61 (s, 6H) 3.62 (m, 1H) 6.18 (d, J=6.25 Hz, 1H) 7.15 (t, J=7.54 Hz, 1H) 7.63 (m, 1H) 7.72 (d, J=8.09 Hz, 1H) 7.98 (dd, J=7.91, 1.29 Hz, 1H).

Workup

  1. customin SYNTHESIS, 22-25, 1988
  2. temperatureheating
  3. custompartitioned between ethyl acetate and water
  4. washThe ethyl acetate layer was washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was chromatographed on silica gel eluting with 95/5 dichloromethane/ethyl acetate

Sources & evidence

ORD record
ord-00d559b3b5374b868e90c64c29437e1e
Source dataset
uspto-grants-2010_02
Patent number
US07662958B2

Reaction notes

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