Cesium carbonate → 1-(4-Fluorophenyl)-6-(methyl(pyridin-3-ylmethyl)amino)-4-oxo-1,4-dihydroquinoline-3-carbonitrile

HRID 1048895Notes

Reaction equation

HRID 1048895 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[CH:7]=[C:6]([C:19]#[N:20])[C:5]2=[O:21].[CH3:22][NH:23][CH2:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([N:23]([CH3:22])[CH2:24][C:25]4[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:11][CH:10]=3)[C:5](=[O:21])[C:6]([C:19]#[N:20])=[CH:7]2)=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 883933-(Methylaminomethyl)pyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 1214479376-Bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carbonitrile

Product 1

HCID 1214478781-(4-Fluorophenyl)-6-(methyl(pyridin-3-ylmethyl)amino)-4-oxo-1,4-dihydroquinoline-3-carbonitrileYield 40.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Compound W (25 mg, 0.073 mmol, 1.0 eq), N-methyl-N-(3-pyridylmethyl)amine (17 mg, 0.15 mmol, 2.0 eq), cesium carbonate (33 mg, 0.10 mmol, 1.4 eq), tris(dibenzylideneacetone)dipalladium(0) (5.3 mg, 0.0058 mmol, 0.080 eq) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (5.1 mg, 0.0087 mmol, 0.12 eq) were dissolved in toluene (0.5 mL) in a sealed vial and heated at 110° C. overnight. The reaction was cooled, filtered over Celite® and washed with 5% methanol in DCM. The organics were concentrated and purified using reverse phase chromatography to afford 11.3 mg (40%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.44-8.42 (m, 2H), 7.70-7.67 (m, 2H), 7.57 (dt, J=7.8, 1.8 Hz, 1H), 7.48 (t, J=8.7 Hz, 2H), 7.33-7.32 (m, 2H), 7.26 (dd, J=9.4, 3.1 Hz, 1H), 6.83 (d, J=9.3 Hz, 1H), 4.72 (s, 2H), 3.1 (s, 3H); ES-MS [M+1]+: 385.2.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered over Celite®
  3. washwashed with 5% methanol in DCM
  4. concentrationThe organics were concentrated
  5. custompurified

Sources & evidence

ORD record
ord-0805d97e10d141049c6dbfa24ed4bb82
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

Loading…