Potassium Carbonate → (R)-N-((S)-1-(2,5-difluoro-4-(2-(trifluoromethyl)pyridin-4-yl)phenyl)ethyl)-2-methylpropane-2-sulfinamide

HRID 57445

反応式

HRID 57445 の反応式
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([C@@H:9]([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH3:10])=[C:4]([F:18])[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+].[F:53][C:54]([F:65])([F:64])[C:55]1[CH:60]=[C:59](B(O)O)[CH:58]=[CH:57][N:56]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:18][C:4]1[CH:3]=[C:2]([C:59]2[CH:58]=[CH:57][N:56]=[C:55]([C:54]([F:65])([F:64])[F:53])[CH:60]=2)[C:7]([F:8])=[CH:6][C:5]=1[C@@H:9]([NH:11][S@@:12]([C:14]([CH3:17])([CH3:16])[CH3:15])=[O:13])[CH3:10]

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateHCID 451588802-(Trifluoromethyl)pyridine-4-boronic acidHCID 90347558(R)-N-((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

生成物 1

HCID 90414875(R)-N-((S)-1-(2,5-difluoro-4-(2-(trifluoromethyl)pyridin-4-yl)phenyl)ethyl)-2-methylpropane-2-sulfinamide

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
110 °C

実験手順

To a solution of (R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (230 mg, 0.676 mmol) in dioxane/H2O (5 mL/1 mL) was added sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxy-[1,1′-biphenyl]-3-sulfonate (34.7 mg, 0.068 mmol), (2-(trifluoromethyl)pyridin-4-yl)boronic acid (194 mg, 1.014 mmol), K2CO3 (234 mg, 1.690 mmol) followed by Pd2dba3 (31.0 mg, 0.034 mmol). The reaction mixture was sealed and heated to 110° C. and stirred for 2 hours. LCMS show complete conversion. The reaction mixture was then cooled to room temperature and diluted with EtOAc (20 mL) and water (10 mL). The aqueous layer was then extracted with EtOAc (2×20 mL). The combined organic was then concentrated. The residue was purified by silica gel chromatography (50% heptane in EtOAc to 10% MeOH in EtOAc) to give product. (0.25 g). LCMS (B) m/z 407.6 (M+H)+

後処理

  1. customThe reaction mixture was sealed
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. extractionThe aqueous layer was then extracted with EtOAc (2×20 mL)
  4. concentrationThe combined organic was then concentrated
  5. customThe residue was purified by silica gel chromatography (50% heptane in EtOAc to 10% MeOH in EtOAc)
  6. customto give product

出典と根拠

ORDレコード
ord-96026f0949044e428cd32fdaf51b7e0a
出典データセット
uspto-grants-2016_09
特許番号
US09434719B2

関連ノート

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