Sodium Carbonate → (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl) oxazolidin-2-one

HRID 539104노트

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HRID 539104 반응식
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[O:22][CH3:23])[CH2:14][O:13][C:12]3=[O:24])=[N:7][C:6]=12.[F:25][C:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]=1[C:41]1[N:45]=[CH:44][N:43]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:42]=1.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>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].O1CCOCC1>[F:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@@H:15]([C:16]5[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=5[O:22][CH3:23])[CH2:14][O:13][C:12]4=[O:24])=[N:7][C:6]=23)[CH:29]=[CH:28][C:27]=1[C:41]1[N:45]=[CH:44][N:43]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[N:42]=1

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034012HCID 67034012, 화합물HCID 67034207(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one

생성물 1

HCID 68088961(S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl) oxazolidin-2-one수율 53.2%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

To a round bottom flask were added (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one (0.103 g, 0.265 mmol), 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (0.144 g, 0.344 mmol), dioxane (2 mL) and 2.0 M Na2CO3 (0.40 mL, 0.80 mmol). The mixture was degassed by bubbling N2 through the solution. Pd2 dba3 (0.012 g, 0.013 mmol) and dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.013 g, 0.027 mmol) were added, and the mixture was heated at 80° C. overnight. The reaction mixture was cooled to ambient temperature, diluted with H2O, and extracted thoroughly with EtOAc and DCM. The combined organic extracts were washed with brine, dried, and concentrated. Purification of the crude material on silica, eluting with 70% EtOAc/hexanes, to provide (S)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-methoxyphenyl)oxazolidin-2-one as a bright yellow solid (0.0848 g, 53%). MS (APCI+) m/z 601 [M+H]+.

후처리

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. extractionextracted thoroughly with EtOAc and DCM
  5. washThe combined organic extracts were washed with brine
  6. customdried
  7. concentrationconcentrated
  8. customPurification of the crude material on silica
  9. washeluting with 70% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-ae209cd93a9e467fb6331395c0cffcaf
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08865726B2

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