Potassium Carbonate → (Rac)-7-fluoro-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline

HRID 69267노트

반응식

HRID 69267 반응식
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.Cl[C:25]1[CH:26]=[CH:27][C:28]2[N:29]([C:31]([CH:34]([C:36]3[CH:37]=[C:38]4[C:43](=[CH:44][C:45]=3[F:46])[N:42]=[CH:41][CH:40]=[CH:39]4)[CH3:35])=[CH:32][N:33]=2)[N:30]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:46][C:45]1[CH:44]=[C:43]2[C:38]([CH:39]=[CH:40][CH:41]=[N:42]2)=[CH:37][C:36]=1[CH:34]([C:31]1[N:29]2[N:30]=[C:25]([C:13]3[CH:12]=[N:11][N:10]([CH2:9][CH2:8][O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)[CH:14]=3)[CH:26]=[CH:27][C:28]2=[N:33][CH:32]=1)[CH3:35]

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 581475216-(1-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)ethyl)-7-fluoroquinolineHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

생성물 1

HCID 68639506(Rac)-7-fluoro-6-[1-(6-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1h-pyrazol-4-yl}-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-quinoline

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 6344Dichloromethane용매HCID 80711,2-Dimethoxyethane용매

실험 절차

To a solution of [2-(tetrahydro-pyran-2-yloxy)-ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (Stage 171.4, 72.5 mg, 0.225 mmol), (rac)-6-[1-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-ethyl]-7-fluoro-quinoline (Stage 255.2, 49 mg, 0.15 mmol), and 2 M K2CO3 (0.203 mL) in DME (1 mL) stirred at 80-90° C. under argon atmosphere was added PdCl2(PPh3)2 (3.2 mg). After 1.5 h and cooling to rt the RM was taken-up in DCM and water, the aqueous phase was extracted with DCM, the combined organic layers were dried over MgSO4, filtered, evaporated to dryness and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=100:0->80:20) to afford the title compound as a white solid (tR 4.14 min (conditions 3), MH+=487.2).

후처리

  1. extractionwater, the aqueous phase was extracted with DCM
  2. dry with materialthe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/MeOH=100:0->80:20)

출처 및 근거

ORD 기록
ord-43937494f7464dc38250a05605bbab51
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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