Triethylamine → 3-[5-(5-Fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one

HRID 1894227노트

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HRID 1894227 반응식
[CH3:1][C:2]1([CH3:20])[O:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][Si](C)(C)C)=[CH:10][N:9]=2)[CH2:3]1.[F:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26](I)[CH:27]=1.CCN(CC)CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:21][C:22]1[CH:27]=[C:26]([C:15]#[C:14][C:11]2[CH:12]=[CH:13][C:8]([N:4]3[CH2:3][C:2]([CH3:20])([CH3:1])[O:6][C:5]3=[O:7])=[N:9][CH:10]=2)[CH:25]=[N:24][CH:23]=1

참가 물질

10

반응물 6

HCID 8471TriethylamineHCID 11776Triphenylphosphine2회HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 184547783-Fluoro-5-iodopyridineHCID 575167285,5-Dimethyl-3-(5-trimethylsilanylethynyl-pyridin-2-yl)-oxazolidin-2-one

생성물 1

HCID 534933613-[5-(5-Fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매2회

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온도
60 °C

실험 절차

5,5-Dimethyl-3-(5-trimethylsilanylethynyl-pyridin-2-yl)-oxazolidin-2-one (Example 29, step 1) (100 mg, 0.35 mmol) was dissolved in THF (3 ml). 3-Fluoro-5-iodopyridine (100 mg, 0.45 mmol, 1.3 equiv.), Et3N (145 μl, 1.04 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (10 mg, 14 μmol, 0.05 equiv.), triphenylphosphine (11 mg, 17 μmol, 0.05 equiv.), triphenylphosphine (3 mg, 10 μmol, 0.03 equiv.) and copper(I)iodide (1 mg, 3.5 μmol, 0.01 equiv.) were added under nitrogen and the mixture was heated to 60° C. TBAF 1M in THF (520 μl, 0.52 mmol, 1.5 equiv.) was added dropwise in 20 minutes at 60° C. The reaction mixture was stirred for 3 hours at 60° C. Sat. NaHCO3 solution was added and the mixture was extracted with dichloromethane. The organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol gradient 100:0 to 90:10). The desired 3-[5-(5-fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one was obtained as a white solid (55 mg, 51% yield), MS: m/e=312.3 (M+H+).

후처리

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol gradient 100:0 to 90:10)

출처 및 근거

ORD 기록
ord-96e5e1a64ea3487e96d2bda8187c82d1
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08513273B2

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