5-Chloro-2,3-difluoropyridine → 2,3-Difluoro-5-(3-methylisothiazol-5-yl)pyridine

HRID 219205

반응식

HRID 219205 반응식
Cl[C:2]1[CH:3]=[C:4]([F:9])[C:5]([F:8])=[N:6][CH:7]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH3:44][C:45]1[CH:49]=[C:48]([Sn](C)(C)C)[S:47][N:46]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:8][C:5]1[C:4]([F:9])=[CH:3][C:2]([C:48]2[S:47][N:46]=[C:45]([CH3:44])[CH:49]=2)=[CH:7][N:6]=1

참가 물질

6

반응물 3

HCID 27832485-Chloro-2,3-difluoropyridineHCID 100383203-Methyl-5-(trimethylstannyl)isothiazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

생성물 1

HCID 675028582,3-Difluoro-5-(3-methylisothiazol-5-yl)pyridine수율 98%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

5-chloro-2,3-difluoropyridine (0.069 ml, 0.67 mmol), X-Phos (0.045 g, 0.094 mmol) and palladium (II) acetate (0.011 g, 0.047 mmol) were combined in 1,4-dioxane (0.2 M, 3.4 mL). To the reaction vessel was added 3-methyl-5-(trimethylstannyl)isothiazole (0.53 g, 2.0 mmol) and, after purging with argon, the reaction was stirred at 100° C. for 2 h and then concentrated in vacuo. The crude material was dissolved in minimal DCM and purified via MPLC (eluting first with 100% EtOAc followed by 20% EtOAc in hexanes -isocratic) to yield 2,3-difluoro-5-(3-methylisothiazol-5-yl)pyridine (0.139 g, 98% yield) as a yellow solid. 2,3-difluoro-5-(3-methylisothiazol-5-yl)pyridine was converted to the title compound using a procedure similar to 1-(4-methyl-6-phenylpyridazin-3-yl)hydrazine.

후처리

  1. customafter purging with argon
  2. concentrationconcentrated in vacuo
  3. dissolutionThe crude material was dissolved in minimal DCM
  4. custompurified via MPLC (eluting first with 100% EtOAc followed by 20% EtOAc in hexanes -isocratic)

출처 및 근거

ORD 기록
ord-d2d3150d936c4ad4bfd41a0242e1af62
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198448B2

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