Potassium Acetate → 6-[(7-Chloro-1-hydroxy-3H-2,1-benzoxaborol-5-yl)-methylsulfonylamino]-5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide

HRID 1424840Notes

Reaction equation

HRID 1424840 reaction equation
Br[C:2]1[C:7]([CH2:8][O:9]COC)=[CH:6][C:5]([N:13]([C:18]2[C:37]([CH:38]3[CH2:40][CH2:39]3)=[CH:36][C:21]3[C:22]([C:32]([NH:34][CH3:35])=[O:33])=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[O:24][C:20]=3[CH:19]=2)[S:14]([CH3:17])(=[O:16])=[O:15])=[CH:4][C:3]=1[Cl:41].C([O-])(=O)C.[K+].[B:47]1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:48]1>O1CCOCC1.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(Cl)Cl>[Cl:41][C:3]1[C:2]2[B:47]([OH:48])[O:9][CH2:8][C:7]=2[CH:6]=[C:5]([N:13]([C:18]2[C:37]([CH:38]3[CH2:39][CH2:40]3)=[CH:36][C:21]3[C:22]([C:32]([NH:34][CH3:35])=[O:33])=[C:23]([C:25]4[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=4)[O:24][C:20]=3[CH:19]=2)[S:14]([CH3:17])(=[O:15])=[O:16])[CH:4]=1

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 122643080HCID 122643080, compound

Product 1

HCID 714949376-[(7-Chloro-1-hydroxy-3H-2,1-benzoxaborol-5-yl)-methylsulfonylamino]-5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 6-(N-(4-bromo-3-chloro-5-((methoxymethoxy)methyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (0.25 g, 0.38 mmol), potassium acetate (0.15 g, 1.50 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.031 g, 0.038 mmol), bis(pinacolato)diboron (0.29 g, 1.13 mmol) in 1,4-Dioxane (3.75 ml) was degassed, purged with nitrogen and heated at 90° C. for 15 h. The reaction mixture was diluted with EtOAc and water, filtered through celite, and evaporated. The brown residue was dissolved in THF (5 mL), and 1M HCl (5 mL) and the solution was heated at 70° C. for 4 h. MeOH (2 mL) was added and the solution was heated at 70° C. for another 15 h and diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (100% EtOAc to 10% MeOH/CH2Cl2) to obtain the title compound as a clear oil. MeOH was added and the precipitate was collected by vacuum filtration, washed with MeOH and dried to afford the title compound (0.0831 g, 39%) as a light tan solid. The filtrate was purified by reverse phase chromatography (5-100% CH3CN/H2O (0.1% formic acid)) to afford an additional batch of the title compound (0.0146 g, 7%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.17 (s, 1H), 8.50 (d, J=4.68 Hz, 1H), 8.09 (s, 1H), 7.94-8.02 (m, 2H), 7.37-7.46 (m, 3H), 7.28 (d, J=1.56 Hz, 1H), 7.22 (s, 1H), 4.96 (s, 2H), 3.47 (s, 3H), 2.84 (d, J=4.59 Hz, 3H), 2.02-2.14 (m, 1H), 0.98 (br. s., 1H), 0.82 (br. s., 2H), 0.49 (br. s., 1H). LCMS (m/z, ES+)=569.2 (M+H+).

Workup

  1. custompurged with nitrogen
  2. additionThe reaction mixture was diluted with EtOAc and water
  3. filtrationfiltered through celite
  4. customevaporated
  5. dissolutionThe brown residue was dissolved in THF (5 mL)
  6. temperature1M HCl (5 mL) and the solution was heated at 70° C. for 4 h
  7. additionMeOH (2 mL) was added
  8. temperaturethe solution was heated at 70° C. for another 15 h
  9. additiondiluted with EtOAc and water
  10. washThe organic layer was washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated
  14. custompurified by silica gel chromatography (100% EtOAc to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-4da904e908b441d0874550bb9efcefd2
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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