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Potassium Carbonate → (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid

HRID 538998
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HRID 538998 반응식
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@@H:15]([CH:16]([CH3:18])[CH3:17])[CH2:14][O:13][C:12]3=[O:19])=[N:7][C:6]=12.CC1(C)C(C)(C)OB([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=2)O1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.CCOC(C)=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]>[CH:16]([C@H:15]1[CH2:14][O:13][C:12](=[O:19])[N:11]1[C:8]1[CH:9]=[CH:10][N:5]2[N:4]=[CH:3][C:2]([C:28]3[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=3)=[C:6]2[N:7]=1)([CH3:18])[CH3:17]
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참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 27346214-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67034128(S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one

생성물 1

HCID 67034480(S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid
수율 45%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

In a vial, a mixture of (S)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-4-isopropyloxazolidin-2-one (Example 1, Step 4; 1.82 g, 5.58 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (2.08 g, 8.37 mmol), and 2 M K2CO3 (8.37 mL, 16.7 mmol) in dioxane (20 mL) was degassed by bubbling N2 for 5 minutes. Pd2 dba3 (0.51 g, 0.56 mmol) and XPHOS (0.266 g, 0.558 mmol) were added and the reaction was capped under N2 and heated at 100° C. After 19 hours, the mixture was cooled to ambient temperature, diluted with EtOAc, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The crude was purified by silica gel flash column chromatography (0-3% MeOH in dichloromethane) to afford 0.92 g (45%) of (S)-4-(5-(4-isopropyl-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)benzoic acid. LCMS (APCI+) m/z 367.4 [M+H]+.

후처리

  1. customwas degassed
  2. customby bubbling N2 for 5 minutes
  3. customthe reaction was capped under N2
  4. temperaturethe mixture was cooled to ambient temperature
  5. washwashed with water and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by silica gel flash column chromatography (0-3% MeOH in dichloromethane)

출처 및 근거

ORD 기록
ord-4e53a554e7b64723a1967699f8d53026
출처 데이터셋
uspto-grants-2014_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08865726B2

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