1,2-Dimethoxyethane → (Rac)-(5,7-difluoro-quinolin-6-yl)-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-methanol

HRID 69237Notes

Reaction equation

HRID 69237 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[C:14]([F:24])=[C:15]4[C:20](=[CH:21][C:22]=3[F:23])[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C([O-])([O-])=O.[Na+].[Na+].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.CCOC(C)=O>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([C:29]4[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[OH:12])=[C:22]([F:23])[CH:21]=[C:20]2[C:15]=1[CH:16]=[CH:17][CH:18]=[N:19]2

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 58147519(6-Chloroimidazo[1,2-b]pyridazin-3-yl)(5,7-difluoroquinolin-6-yl)methanol

Product 1

HCID 68640982(Rac)-(5,7-difluoro-quinolin-6-yl)-[6-(1-methyl-1h-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-methanol

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

(rac)-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-(5,7-difluoro-quinolin-6-yl)-methanol (Stage 171.3, 1.8 g, 5.19 mmol) was introduced in a microwave reactor together with 1-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (1.08 g, 5.19 mmol), tetrakis(triphenylphosphine)-palladium (300 mg, 0.26 mmol), 2 M Na2CO3 (9.34 mL) and DME (20 mL). The mixture was heated at 150° C. under microwave irradiation for 50 min. The RM was taken up with EtOAc and washed with 10% Na2CO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was triturated with Et2O and the precipitate was filtered off to give the title compound as a black solid (tR 0.8 min (conditions 2), MH+=393)

Workup

  1. washwashed with 10% Na2CO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was triturated with Et2O
  6. filtrationthe precipitate was filtered off

Sources & evidence

ORD record
ord-201dfbaf59554d55879f90002b554c57
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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