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

HRID 69263

反応式

HRID 69263 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 86584982Sodium bicarbonate ethyl acetate溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-679fa1e96009440dbb151f8235dbc072
出典データセット
uspto-grants-2014_09
特許番号
US08822468B2

関連ノート

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