3-Methyl-5-(trimethylstannyl)isothiazole → 4-((8-Fluoro-6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline

HRID 219155

반응식

HRID 219155 반응식
Cl[C:2]1[CH:3]=[C:4]([F:25])[C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[CH:7]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[CH3:60][C:61]1[CH:65]=[C:64]([Sn](C)(C)C)[S:63][N:62]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[F:25][C:4]1[C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[CH:7]=[C:2]([C:64]2[S:63][N:62]=[C:61]([CH3:60])[CH:65]=2)[CH:3]=1

참가 물질

6

반응물 3

HCID 100383203-Methyl-5-(trimethylstannyl)isothiazole2회HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2회HCID 675022054-((6-Chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline

생성물 1

HCID 576911514-((8-Fluoro-6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline수율 51.1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매2회HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

Dioxane (3.6 mL) was added to 4-((6-chloro-8-fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methoxy)-7-methoxyquinoline (175 mg, 488 μmol), X-Phos (32.6 mg, 68.3 μmol), 3-methyl-5-(trimethylstannyl)isothiazole (153 mg, 585 μmol), palladium acetate (7.67 mg, 34.1 μmol). The flask was purged with argon and sealed. The reaction mixture was stirred at 80° C. for 2d. More X-Phos (32.6 mg, 68.3 μmol), palladium acetate (7.67 mg, 34.1 μmol) and 3-methyl-5-(trimethylstannyl)isothiazole (153 mg, 585 μmol) were added and stirring was continued at 80° C. overnight. The reaction mixture was cooled at RT, concentrated in vacuo and urified by MPLC (CH2Cl2/MeOH: 100/0 to 90/10). Further purification by MPLC (ISCO, EtOAc/MeOH:9/1, isocratic) afforded the title compound (105 mg, 51% yield). MS m/z=422.0 [M+H]+. Calc'd for C21H16FN5O2S: 421.46

후처리

  1. customThe flask was purged with argon
  2. customsealed
  3. stirringstirring
  4. temperatureThe reaction mixture was cooled at RT
  5. concentrationconcentrated in vacuo
  6. customFurther purification by MPLC (ISCO, EtOAc/MeOH:9/1, isocratic)

출처 및 근거

ORD 기록
ord-c797341a0e6840289166d954331465dd
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08198448B2

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