Potassium Carbonate → 5-(6-chloro-5-formylpyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595762Notes

Reaction equation

HRID 595762 reaction equation
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[O:19][C:20]3[CH:30]=[C:29]([N:31]([CH3:36])[S:32]([CH3:35])(=[O:34])=[O:33])[C:28](B4OC(C)(C)C(C)(C)O4)=[CH:27][C:21]=3[C:22]=2[C:23]([NH:25][CH3:26])=[O:24])=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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]>[Cl:1][C:2]1[N:9]=[C:8]([C:28]2[C:29]([N:31]([CH3:36])[S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][C:20]3[O:19][C:18]([C:15]4[CH:16]=[CH:17][C:12]([F:11])=[CH:13][CH:14]=4)=[C:22]([C:23]([NH:25][CH3:26])=[O:24])[C:21]=3[CH:27]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 122593832,6-Dichloropyridine-3-carbaldehydeHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide

Product 1

HCID 903324705-(6-chloro-5-formylpyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 86.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of 2,6-dichloronicotinaldehyde (315 mg, 1.79 mmol) and 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (600 mg, 1.19 mmol) in 1,4-dioxane (8 mL) and water (300 μL) was added K2CO3 (330 mg, 2.40 mmol) and Pd(dppf)Cl2 (175 mg, 0.24 mmol) under N2 protection. The resulting mixture was heated to 80° C. and stirred at this temperature overnight. The reaction was cooled, filtered through a pad of celite and washed with ethyl acetate. The combined filtrate was evaporated in vacuo. The resulting residue was purified using column chromatography (eluted with 0-30% EtOAc/DCM) to provide 5-(6-chloro-5-formylpyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (530 mg, yield: 86%) MS (M+H)+: 516.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered through a pad of celite
  3. washwashed with ethyl acetate
  4. customThe combined filtrate was evaporated in vacuo
  5. customThe resulting residue was purified
  6. washcolumn chromatography (eluted with 0-30% EtOAc/DCM)

Sources & evidence

ORD record
ord-16b807a693854fa8a20c44a7a8574b44
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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