Potassium Carbonate → 5-(6-chloro-5-(1-(hydroxymethyl)cyclopropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 595776Notes

Reaction equation

HRID 595776 reaction equation
Br[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]2([CH2:12][OH:13])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][C:23]3[CH:33]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[C:31](B(O)O)=[CH:30][C:24]=3[C:25]=2[C:26](=[O:29])[NH:27][CH3:28])=[CH:17][CH:16]=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:8][C:6]1[N:7]=[C:2]([C:31]2[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:33][C:23]3[O:22][C:21]([C:18]4[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=4)=[C:25]([C:26]([NH:27][CH3:28])=[O:29])[C:24]=3[CH:30]=2)[CH:3]=[CH:4][C:5]=1[C:9]1([CH2:12][OH:13])[CH2:11][CH2:10]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 90332474(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acidHCID 90332508(1-(6-Bromo-2-chloropyridin-3-yl)cyclopropyl)methanol

Product 1

HCID 903324785-(6-chloro-5-(1-(hydroxymethyl)cyclopropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideYield 37.6%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
70 °C

Procedure

To a solution of (1-(6-bromo-2-chloropyridin-3-yl)cyclopropyl)methanol (100 mg, 0.381 mmol) and (2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)boronic acid (160 mg, 0.381 mmol) in 1,4-Dioxane (2 mL) and water (20 μL) was added K2CO3 (105 mg, 0.762 mmol) and Pd(dppf)Cl2 (55 mg, 0.075 mmol). The mixture was heated to 70° C. and stirred overnight. Filtration through a pad of celite removed the solid. After washing with ethyl acetate, the combined filtrate was concentrated in vacuo. Preparative TLC gave 5-(6-chloro-5-(1-(hydroxymethyl)cyclopropyl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (80 mg, yield: 37.6%) MS (M+H)+: 559.

Workup

  1. filtrationFiltration through a pad of celite
  2. customremoved the solid
  3. washAfter washing with ethyl acetate
  4. concentrationthe combined filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-cc863e542c5e45ef9ba1232402728801
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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