Cesium carbonate → 6-Chloro-4-[(4,6-dimethyl-2-pyridinyl)amino]-3-pyridinecarbonitrile

HRID 878397Notes

Reaction equation

HRID 878397 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[N:9])=[C:4](I)[CH:3]=1.[CH3:11][C:12]1[CH:17]=[C:16]([CH3:18])[N:15]=[C:14]([NH2:19])[CH:13]=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+]>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]>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]#[N:9])=[C:4]([NH:19][C:14]2[CH:13]=[C:12]([CH3:11])[CH:17]=[C:16]([CH3:18])[N:15]=2)[CH:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 215072-Amino-4,6-dimethylpyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 575169126-Chloro-4-iodopyridine-3-carbonitrile

Product 1

HCID 894867076-Chloro-4-[(4,6-dimethyl-2-pyridinyl)amino]-3-pyridinecarbonitrile

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
50 °C

Procedure

A mixture of 6-chloro-4-iodopyridine-3-carbonitrile (CAS: 1061357-83-2) (5.0 g, 19 mmol), 4,6-dimethylpyridin-2-amine (2.31 g, 18.9 mmol), Xantphos (2.2 g, 3.8 mmol), Pd2(dba)3 (1.73 g, 1.89 mmol), and cesium carbonate (8.62 g, 26.5 mmol) was purged with nitrogen. Dioxane (45 mL) was added, and the reaction mixture was heated to 50° C. After 1 hour, the mixture was allowed to cool to room temperature, filtered through a pad of CELITE, and washed with dichloromethane. The mixture was concentrated under reduced pressure, diluted with water, and extracted with dichloromethane (2×20 mL). The organics were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to provide 6-chloro-4-[(4,6-dimethylpyridin-2-yl)amino]pyridine-3-carbonitrile. MS ESI calc'd. for C13H12ClN4 [M+H]+ 259. found 259. 1H NMR (500 MHz, DMSO-d6) δ 9.70 (s, 1H), 8.57 (s, 1H), 8.31 (s, 1H), 6.92 (s, 1H), 6.80 (s, 1H), 2.37 (s, 3H), 2.25 (s, 3H).

Workup

  1. customwas purged with nitrogen
  2. additionDioxane (45 mL) was added
  3. temperatureto cool to room temperature
  4. filtrationfiltered through a pad of CELITE
  5. washwashed with dichloromethane
  6. concentrationThe mixture was concentrated under reduced pressure
  7. additiondiluted with water
  8. extractionextracted with dichloromethane (2×20 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-9a3bdad063d64680b806eb46dfb4b19f
Source dataset
uspto-grants-2015_03
Patent number
US08987456B2

Reaction notes

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