Tributylphosphine → 6-(benzylthio)-1-(6-(3-fluorophenyl)-4-methoxypyridin-3-yl)quinolin-2(1H)-one

HRID 1504372Notes

Reaction equation

HRID 1504372 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[CH:11][C:12]([NH:22][C:23]2[CH:24]=[N:25][C:26]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)=[CH:27][C:28]=2[O:29][CH3:30])=[C:13](/[CH:15]=[CH:16]/[C:17]([O:19]CC)=O)[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.C[O-].[Na+]>CO>[CH2:1]([S:8][C:9]1[CH:14]=[C:13]2[C:12](=[CH:11][CH:10]=1)[N:22]([C:23]1[CH:24]=[N:25][C:26]([C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[CH:32]=3)=[CH:27][C:28]=1[O:29][CH3:30])[C:17](=[O:19])[CH:16]=[CH:15]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 10942334Sodium MethoxideHCID 117739607(E)-ethyl 3-(5-(benzylthio)-2-((6-(3-fluorophenyl)-4-methoxypyridin-3-yl)amino)phenyl)acrylate

Product 1

HCID 1177368906-(benzylthio)-1-(6-(3-fluorophenyl)-4-methoxypyridin-3-yl)quinolin-2(1H)-oneYield 33.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A MeOH solution of (E)-ethyl 3-(5-(benzylthio)-2-((6-(3-fluorophenyl)-4-methoxypyridin-3-yl)amino)phenyl)acrylate (0.615 g, 1.195 mmol) and tributylphosphine (0.060 ml, 0.239 mmol) in a 40-mL vial was stirred overnight at 70° C. Sodium methoxide, 25 wt % solution in methanol (0.106 ml, 0.478 mmol) was then added. After stirring for 2 h, the reaction was concentrated under a stream of N2 and purified via column chromatography (50 g Snap Ultra column, 0% to 100% EtOAc/hept) to afford 6-(benzylthio)-1-(6-(3-fluorophenyl)-4-methoxypyridin-3-yl)quinolin-2(1H)-one (186.7 mg, 0.398 mmol, 33.3% yield) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.92 (s, 3 H) 4.26 (s, 2 H) 6.60 (d, J=8.81 Hz, 1 H) 6.72 (d, J=9.53 Hz, 1 H) 7.20-7.39 (m, 6 H) 7.42 (dd, J=8.81, 2.18 Hz, 1 H) 7.61 (dd, J=8.03, 1.92 Hz, 1 H) 7.83 (d, J=2.18 Hz, 1H) 7.90 (s, 1H) 8.00 (d, J=9.43 Hz, 1 H) 8.04-8.09 (m, 1 H) 8.09-8.13 (m, 1 H) 8.45 (s, 1 H). m/z (ESI) 469.2 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated under a stream of N2
  2. custompurified via column chromatography (50 g Snap Ultra column, 0% to 100% EtOAc/hept)

Sources & evidence

ORD record
ord-a485deaf9c3d4ef18dd9419c7afe1ad8
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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