Sodium Carbonate → N-(6-(6-Chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162486Notes

Reaction equation

HRID 1162486 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH:19]([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.Cl[C:32]1[CH:33]=[CH:34][C:35]2[N:36]([CH:38]=[C:39]([NH:41][C:42](=[O:44])[CH3:43])[N:40]=2)[N:37]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:32]2[CH:33]=[CH:34][C:35]3[N:36]([CH:38]=[C:39]([NH:41][C:42](=[O:44])[CH3:43])[N:40]=3)[N:37]=2)=[CH:6][C:7]=1[NH:8][S:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH:19]([F:20])[F:21])[CH:13]=1)(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 57416507N-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-3-(difluoromethoxy)benzene-1-sulfonamideHCID 59519510N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44125259N-(6-(6-Chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamideYield 82.9%

Reagents, catalysts & solvents 2

HCID 178478230HCID 178478230, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A sealable vial was charged with N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)-3-(difluoromethoxy)benzenesulfonamide (765.9 mg, 1663 μmol), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (291.8 mg, 1385 μmol, Example 1, Step 4), dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (53.76 mg, 96.98 μmol, Strem Chemical, Inc., Newburyport, Mass.) and sodium carbonate (293.7 mg, 2771 μmol). The vial was sealed with a septum cap and dioxane (2 mL, 1 M) and water (1 mL, 2 M) were added via syringe. The mixture was sparged 10 min with N2, then heated at 90° C. for 18 h. The solution was cooled to rt, and concentrated for purification by MPLC (CombiFlash® Companion®, Teledyne Isco, Lincoln, Nebr.). The crude residue was taken up in minimal CH2Cl2/MeOH and absorbed onto a 25 g silica loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (80 g) (Teledyne Isco, Lincoln, Nebr.) using a gradient of 1% MeOH in CH2Cl2 to 10% MeOH in CH2Cl2 to afford N-(6-(6-chloro-5-(3-(difluoromethoxy)phenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (584.0 mg, 82.83% yield) as a brown solid. LCMS (ESI) m/z: 509.1 (M+1).

Workup

  1. customThe vial was sealed with a septum
  2. customcap
  3. customThe mixture was sparged 10 min with N2
  4. temperatureThe solution was cooled to rt
  5. concentrationconcentrated for purification by MPLC (CombiFlash® Companion®, Teledyne Isco, Lincoln, Nebr.)
  6. customabsorbed onto a 25 g silica loading cartridge

Sources & evidence

ORD record
ord-f964574b8d904eb6b27bca15e6ee0524
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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