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

HRID 57445

반응식

HRID 57445 반응식
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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 218864351,4-Dioxane--water (1/1)용매

반응 조건

온도
110 °C

실험 절차

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)+

후처리

  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

출처 및 근거

ORD 기록
ord-96026f0949044e428cd32fdaf51b7e0a
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434719B2

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