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

HRID 552097Notes

Reaction equation

HRID 552097 reaction equation
[CH:1]1([CH2:4][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])[CH2:3][CH2:2]1.N1C=CC=CC=1.S(OC)(O[C:28](SC)([S:31][CH3:32])[S:29][CH3:30])(=O)=O>O1CCOCC1>[CH3:30][S:29][C:28]([S:31][CH3:32])=[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][CH2:4][CH:1]2[CH2:2][CH2:3]2)[C:7]1=[O:17]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24976308Tris(methylthio)methyl methyl sulfate2×HCID 670640181-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one

Product 1

HCID 670636773-[bis(methylthio)methylene]-1-[(cyclopropylmethyl)amino]quinoline-2,4(1H,3H)-dioneYield 60%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To the suspension of 1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one (984.4 mg, 4.28 mmol) in 1,4-dioxane (40 mL) was added pyridine (2.8 mL, 34.6 mmol) and tris(methylthio)methyl methyl sulfate (prepared using the procedures in SYNTHESIS, 22-25, 1988; M. Barbero, S. Cadamuro, I. Degani, R. Fochi, A. Gatti, V. Regondi) (2.26 g, 8.55 mmol) at room temperature. The suspension was put in a preheated oil bath at 55° C. and stirred for 15 minutes. To the solution was added another portion of tris(methylthio)methyl methyl sulfate (2.26 g, 8.55 mmol) and the mixture was stirred at 55° C. for 15 minutes and cooled to room temperature. The mixture was concentrated in vacuo and the residue was diluted with dichloromethane and loaded on a silica gel column and eluted with dichloromethane, 2% ethyl acetate/dichloromethane and then 5% ethyl acetate/dichloromethane to give 3-[bis(methylthio)methylene]-1-[(cyclopropylmethyl)amino] quinoline-2,4(1H,3H)-dione (852.1 mg, 60%). 1H NMR (300 MHz, DMSO-d6) δ 0.15 (m, 2 H) 0.42 (m, 2 H) 0.98 (m, 1 H) 2.61 (s, 6 H) 2.73 (t, J=6.43 Hz, 2 H) 6.05 (t, J=5.88 Hz, 1 H) 7.15 (m, 1 H) 7.64 (m, 1 H) 7.76 (d, J=8.09 Hz, 1 H) 7.98 (m, 1 H).

Workup

  1. customprepared
  2. customin SYNTHESIS, 22-25, 1988
  3. customat room temperature
  4. customThe suspension was put in a preheated oil bath at 55° C.
  5. stirringthe mixture was stirred at 55° C. for 15 minutes
  6. concentrationThe mixture was concentrated in vacuo
  7. additionthe residue was diluted with dichloromethane
  8. washeluted with dichloromethane, 2% ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-e06ac85cd57a420eb6095915974afd42
Source dataset
uspto-grants-2011_05
Patent number
US07951800B2

Reaction notes

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