Potassium Carbonate → 6-Chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine

HRID 1483779

Reaction equation

HRID 1483779 reaction equation
[Br:1][C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[F:12][C:13]([F:25])([F:24])[O:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:13]([F:12])([F:24])[F:25])[CH:16]=3)=[CH:3][N:4]=2)[N:7]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 2

HCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 593798616-Chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazineYield 94.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

3-bromo-6-chloroimidazo[1,2-b]pyridazine was prepared according to procedures described in U.S. Pat. No. 7,750,007, which is hereby incorporated by reference in its entirety. To a solution of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (5 g, 21.5 mmol) and 3-(trifluoromethoxy)phenylboronic acid (4.43 g, 21.5 mmol) in dioxane/H2O (100 mL, 4:1) was added K2CO3 (6.8 g, 64.5 mmol) and Pd(PPh3)4 (1.9 g, 2.58 mmol), the mixture was stirred at 110° C. for 3 h. The solution was concentrated, partitioned in EtOAc/H2O. The aqueous layer was washed with EtOAc (50 mL) for 3 times. The collected organic layers were dried over Na2SO4, concentrated and purified by column chromatography to give compound 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (3.2 g, with 63% purity, yield 30%) as a brown solid.

Workup

  1. concentrationThe solution was concentrated
  2. custompartitioned in EtOAc/H2O
  3. washThe aqueous layer was washed with EtOAc (50 mL) for 3 times
  4. dry with materialThe collected organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-891934e07fa440c5b3f7061d9f74c1be
Source dataset
uspto-grants-2016_08
Patent number
US09416132B2

Linked notes

Loading…