Ethyl Acetate → 4-{4-[3-(5,7-Difluoro-quinolin-6-yl methyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 69259Notes

Reaction equation

HRID 69259 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[C:13]([F:23])=[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:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([N:37]2[CH:41]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:39]=[N:38]2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][CH:34]([N:37]2[CH:41]=[C:40]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]([C:8]([CH2:11][C:12]5[C:13]([F:23])=[C:14]6[C:19](=[CH:20][C:21]=5[F:22])[N:18]=[CH:17][CH:16]=[CH:15]6)=[CH:9][N:10]=4)[N:7]=3)[CH:39]=[N:38]2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 581475266-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinoline

Product 1

HCID 579173924-{4-[3-(5,7-Difluoro-quinolin-6-yl methyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

6-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinoline (Stage 171.2, 264 mg, 0.798 mmol) was dissolved in DME (2.5 mL) in a microwave reactor with 4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (see Stage 180.1, 301 mg, 0.798 mmol), and a solution of 2 M Na2CO3 (1.44 mL). Then tetrakis-(triphenylphosphine)-palladium (46.1 mg, 0.040 mmol) was added and the RM was heated at 150° C. for 5 min under microwave irradiations. It was then taken up with EtOAc and washed with 10% Na2CO3 sol. and brine. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM) to afford after evaporation of the solvent the title compound as a pale yellow solid (tR 1.3 min (conditions 2), MH+=546).

Workup

  1. washwashed with 10% Na2CO3 sol. and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. customthe solvent was removed
  4. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM)
  5. customto afford
  6. customafter evaporation of the solvent the title compound as a pale yellow solid (tR 1.3 min (conditions 2), MH+=546)

Sources & evidence

ORD record
ord-1a9578272db04cac9442663215acbf2f
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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