Lithium Chloride → N-(5-Chloropyridin-2-yl)-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]-5-(4-pyridinyl)-benzamide

HRID 1247145Notes

Reaction equation

HRID 1247145 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14](I)[CH:13]=[CH:12][C:11]=2[NH:17][C:18]([CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[O:19])=[N:6][CH:7]=1.[Cl-].[Li+].C([Sn](CCCC)(CCCC)[C:37]1[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=1)CCC>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[C:10]2[CH:15]=[C:14]([C:37]3[CH:42]=[CH:41][N:40]=[CH:39][CH:38]=3)[CH:13]=[CH:12][C:11]=2[NH:17][C:18]([CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[O:19])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 27373184-(Tri-n-butylstannyl)pyridineHCID 21906277N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide

Product 1

HCID 21906553N-(5-Chloropyridin-2-yl)-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]-5-(4-pyridinyl)-benzamideYield 20%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirring solution of N-(5-chloropyridin-2-yl)-5-iodo-2-[(1-isopropylpiperidin-4-ylcarbonyl)amino]benzamide (0.52 g, 0.98 mmol), dichlorobis(triphenylphosphine)palladium(II) (34 mg, 0.05 mmol), and lithium chloride (0.15 g, 3.56 mmol) in 1,4-dioxane (5 mL) was added 4-(tributylstannyl)pyridine (1.16 g, 3.14 mmol) and dioxane (5 mL). The reaction mixture was heated to reflux, stirred overnight, and then filtered through diatomaceous earth. The filtrate was partitioned between 3:1 chloroform:isopropanol and saturated aqueous sodium bicarbonate, and the layers separated. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography over silica gel, eluting with a step gradient of 10–25% 2 M ammonia/methanol solution in dichloromethane. The chromatography product was recrystallized from methanol and ethyl acetate to give 47 mg (20%) of a white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. filtrationfiltered through diatomaceous earth
  4. customThe filtrate was partitioned between 3:1 chloroform
  5. customisopropanol and saturated aqueous sodium bicarbonate, and the layers separated
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography over silica gel
  10. washeluting with a step gradient of 10–25% 2 M ammonia/methanol solution in dichloromethane
  11. customThe chromatography product was recrystallized from methanol and ethyl acetate

Sources & evidence

ORD record
ord-4c2d2c923d7140548a50e630b222c1ab
Source dataset
uspto-grants-2006_10
Patent number
US07129245B2

Reaction notes

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