Sodium Carbonate → Ethyl 5-(2-chloro-5-(3-chloro-6-(cyanomethyl)pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522114Notes

Reaction equation

HRID 522114 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][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]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1)=[O:5].[Cl:36][C:37]1[CH:38]=[CH:39][C:40]([CH2:44][C:45]#[N:46])=[N:41][C:42]=1Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([C:42]2[C:37]([Cl:36])=[CH:38][CH:39]=[C:40]([CH2:44][C:45]#[N:46])[N:41]=2)=[CH:23][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1)=[O:5]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 1184971842-(5,6-Dichloropyridin-2-yl)acetonitrileHCID 123572737ethyl 5-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

Product 1

HCID 118497146Ethyl 5-(2-chloro-5-(3-chloro-6-(cyanomethyl)pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylateYield 51.6%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of ethyl 5-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate (Preparation 5, 1.01 g, 1.34 mmol) and 2-(5,6-dichloropyridin-2-yl)acetonitrile (Preparation 59, 300 mg, 1.60 mmol) in dioxane (10 mL) was added Na2CO3 (213 mg, 2.01 mmol), water (1 drop) and Pd(PPh3)4 (144 mg, 0.134 mmol). The reaction was further degassed and heated to 80° C. for 1 hour. Further water (1 mL) was added and heating continued for 5 hours before cooling to room temperature. The reaction was filtered through Celite washing through with EtOAc, and concentrated in vacuo. The residue was purified using reverse phase column chromatography eluting with 0-100% MeCN in water with 0.1% formic acid to afford the title compound (360 mg, 49%).

Workup

  1. customThe reaction was further degassed
  2. additionFurther water (1 mL) was added
  3. temperatureheating
  4. temperaturebefore cooling to room temperature
  5. filtrationThe reaction was filtered through Celite
  6. washwashing through with EtOAc
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified
  9. washeluting with 0-100% MeCN in water with 0.1% formic acid

Sources & evidence

ORD record
ord-c2d1c8e3b18a4fa6accd1b9d692a4a34
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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