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

HRID 69263

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-679fa1e96009440dbb151f8235dbc072
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822468B2

Linked notes

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