Cesium carbonate → 5-[(2,4-Dimethoxybenzyl)amino]-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile

HRID 1504755Notes

Reaction equation

HRID 1504755 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=2)[C:5]([C:8]#[N:9])=[N:6][CH:7]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:67][O:68][C:69]1[CH:76]=[C:75]([O:77][CH3:78])[CH:74]=[CH:73][C:70]=1[CH2:71][NH2:72]>O1CCOCC1.C(OCC)(=O)C.O.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]>[CH3:67][O:68][C:69]1[CH:76]=[C:75]([O:77][CH3:78])[CH:74]=[CH:73][C:70]=1[CH2:71][NH:72][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[N:12]=2)[C:5]([C:8]#[N:9])=[N:6][CH:7]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 5972502,4-DimethoxybenzylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867316505-Bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile

Product 1

HCID 867316525-[(2,4-Dimethoxybenzyl)amino]-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a flask was added 5-bromo-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile (PrepEx 1.4) (500 mg, 1.65 mmol), Xantphos (95 mg, 0.17 mmol), Pd2(dba)3 (121 mg, 0.133 mmol) and cesium carbonate (1.08 g, 3.30 mmol). A solution of 2,4-Dimethoxybenzylamine (276 mg, 1.65 mmol) in degassed dioxane (16.5 mL) was added to the flask. The reaction was heated to 100° C. for one hour. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and water, and the organic layer was separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-40% ethyl acetate/hexanes, linear gradient) to afford 5-[(2,4-dimethoxybenzyl)amino]-3-[(4,6-dimethylpyridin-2-yl)amino]pyridine-2-carbonitrile. MS ESI calc'd for C22H24N5O2 [M+H]+ 390. found 390. 1H NMR (500 MHz, DMSO-d6) δ 8.62 (s, 1H), 7.71 (d, J=2.3 Hz, 1H), 7.43 (d, J=2.3 Hz, 1H), 7.21 (t, J=5.7 Hz, 1H), 7.08 (d, J=8.3 Hz, 1H), 6.57 (s, 1H), 6.54 (d, J=2.3 Hz, 1H), 6.53 (s, 1H), 6.45 (dd, J=2.3 Hz, 8.3 Hz, 1H), 4.16 (d, J=5.8 Hz, 2H), 3.73 (s, 3H), 3.70 (s, 3H), 2.18 (s, 3H), 2.15 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe organic layer was separated
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (0-40% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-5eed3264f58845f79576a76472aa658d
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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