Potassium Acetate → 6-((7-Chloro-1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)(methylsulfonyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide

HRID 2272338ノート

反応式

HRID 2272338 の反応式
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

参加物

6

反応物 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 122643080HCID 122643080、化合物

生成物 1

HCID 714949376-((7-Chloro-1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)(methylsulfonyl)amino)-5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-1-benzofuran-3-carboxamide

試薬・触媒・溶媒 2

HCID 178418807HCID 178418807、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-c34a4adc611d40fa92c7c38327aa524a
出典データセット
uspto-grants-2015_09
特許番号
US09119868B2

反応ノート

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