Potassium Carbonate → 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(3-fluoro-6-(methoxymethyl)pyridin-2-yl)benzamide

HRID 522102Notes

Reaction equation

HRID 522102 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].Cl[C:34]1[C:39]([F:40])=[CH:38][CH:37]=[C:36]([CH2:41][O:42][CH3:43])[N:35]=1.C(=O)([O-])[O-].[K+].[K+]>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:23]=[CH:22][C:21]([C:34]2[C:39]([F:40])=[CH:38][CH:37]=[C:36]([CH2:41][O:42][CH3:43])[N:35]=2)=[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]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 1184970432-Chloro-3-fluoro-6-(methoxymethyl)pyridineHCID 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 1184970782-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(3-fluoro-6-(methoxymethyl)pyridin-2-yl)benzamideYield 75.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a degassed 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, 325 mg, 0.72 mmol), 2-chloro-3-fluoro-6-(methoxymethyl)pyridine (Preparation 52, 191 mg, 1.09 mmol) and potassium carbonate (200 mg, 1.45 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added Pd(PPh3)4 (83 mg, 0.072 mmol) and the reaction was heated to 80° C. for 18 hours. The reaction was cooled and concentrated in vacuo. The resulting residue was partitioned between EtOAc (15 mL) and water (15 mL). The aqueous layer was extracted with EtOAc (2×15 mL) and the organic extracts were combined, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 1:1 EtOAc in heptanes to afford the title compound (250 mg, 75%).

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was partitioned between EtOAc (15 mL) and water (15 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (2×15 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified
  8. washeluting with 1:1 EtOAc in heptanes

Sources & evidence

ORD record
ord-544ed3ab47e84a3ca408cfc7dce3a414
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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