Sodium Carbonate → 5-(6-acetamidopyridin-2-yl)-2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)benzamide

HRID 522101Notes

Reaction equation

HRID 522101 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=1)=[O:5].Br[C:34]1[N:39]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:41]([NH:40][C:38]1[N:39]=[C:34]([C:21]2[CH:22]=[CH:23][C:2]([Cl:1])=[C:3]([CH:20]=2)[C:4]([NH:6][C:7]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=2)=[O:5])[CH:35]=[CH:36][CH:37]=1)(=[O:43])[CH3:42]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 10353221N-(6-bromopyridin-2-yl)acetamideHCID 1238597502-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 1184971625-(6-acetamidopyridin-2-yl)-2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)benzamideYield 46%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Preparation 7, 0.5 mmol) in dioxane (5 mL) was added N-(6-bromopyridin-2-yl)acetamide (118 mg, 0.55 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (41 mg, 0.05 mmol), sodium carbonate (183 mg, 1.72 mmol) and water (1 mL). The reaction was heated to 100° C. for 18 hours. The reaction was allowed to cool to room temperature and diluted with ethyl acetate (10 mL) and water (10 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 40-50% ethyl acetate in heptanes to afford the title compound as a yellow solid (104 mg, 46%).

Workup

  1. temperatureto cool to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with 40-50% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-5f102ee65fb440878dfd0a77c54addde
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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