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 539104ノート

反応式

HRID 539104 の反応式
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

参加物

8

反応物 4

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

生成物 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-one収率 53.2%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-ae209cd93a9e467fb6331395c0cffcaf
出典データセット
uspto-grants-2014_10
特許番号
US08865726B2

反応ノート

読み込み中…