Potassium Carbonate → 7-fluoro-6-[6-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

HRID 69263

반응식

HRID 69263 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.C(OC([N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:32]=[N:31]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>COCCOC.CCOC(C)=O.C([O-])(O)=O.[Na+].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:22][C:21]1[CH:20]=[C:19]2[C:14]([CH:15]=[CH:16][CH:17]=[N:18]2)=[CH:13][C:12]=1[CH2:11][C:8]1[N:6]2[N:7]=[C:2]([C:33]3[CH:34]=[N:30][NH:31][CH:32]=3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 581475166-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline

생성물 1

HCID 1361394287-fluoro-6-[6-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 80711,2-Dimethoxyethane용매HCID 86584982Sodium bicarbonate ethyl acetate용매

반응 조건

온도
90 °C

실험 절차

A mixture of 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline (Stage 173.1, 50 mg, 0.160 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (70.5 mg, 0.240 mmol), Pd(PPh3)2Cl2 (5.61 mg) and 2 M K2CO3 (0.216 mL, 0.423 mmol) in DME (1 mL) was stirred at 90° C. for 3 h. The Boc protecting group felt off during the course of the reaction. The mixture was diluted with EtOAc/NaHCO3 and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered, evaporated to dryness and the residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 19:1=100:0->0:100) to afford the title compound (tR 3.22 min (conditions 3), MH+=345.1).

후처리

  1. extractionextracted with EtOAc
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customthe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, DCM/DCM/MeOH 19:1=100:0->0:100)

출처 및 근거

ORD 기록
ord-679fa1e96009440dbb151f8235dbc072
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822468B2

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