Cesium carbonate → Ethyl 1-(4-fluorophenyl)-6-(methyl(pyridin-3-ylmethyl)amino)-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 1048882Notes

Reaction equation

HRID 1048882 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]([O:21][CH2:22][CH3:23])=[O:20])[C:5]2=[O:24].[CH3:25][NH:26][CH2:27][C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=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:14]=[CH:13][C:12]([N:8]2[C:9]3[C:4](=[CH:3][C:2]([N:26]([CH3:25])[CH2:27][C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)=[CH:11][CH:10]=3)[C:5](=[O:24])[C:6]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:7]2)=[CH:17][CH:16]=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 121447944Ethyl 6-bromo-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 121447955Ethyl 1-(4-fluorophenyl)-6-(methyl(pyridin-3-ylmethyl)amino)-4-oxo-1,4-dihydroquinoline-3-carboxylateYield 33%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

Compound D (75 mg, 0.19 mmol, 1.0 eq), N-methyl-N-(3-pyridylmethyl)amine (47 mg, 0.38 mmol, 2.0 eq), cesium carbonate (88 mg, 0.27 mmol, 1.4 eq), tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.015 mmol, 0.080 eq) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (13 mg, 0.023 mmol, 0.12 eq) were dissolved in toluene (1.9 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 27 mg (33%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.44 (s, 2H), 8.28 (s, 1H), 7.68 (dd, J=6.9, 4.9 Hz, 2H), 7.58 (d, J=7.8 Hz, 1H), 7.47 (t, J=8.7 Hz, 2H), 7.40 (d, J=3.0 Hz, 1H), 7.34-7.30 (m, 1H), 7.21 (dd, J=9.3, 3.0 Hz, 1H), 6.80 (d, J=9.3 Hz, 1H), 4.70 (s, 2H), 4.17 (q, J=7.1 Hz, 2H), 3.12 (s, 3H), 1.23 (t, J=7.1 Hz, 3H); ES-MS [M+1]+: 432.3.

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-2fa6c42ef5334adb8d0036ac10abd6bf
Source dataset
uspto-grants-2016_07
Patent number
US09382208B1

Reaction notes

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