Sodium Carbonate → HCID 44124988, compound

HRID 1162493Notes

Reaction equation

HRID 1162493 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.OC(C(F)(F)F)=O.Cl[C:36]1[CH:37]=[CH:38][C:39]2[N:40]([C:42]([C:49]3[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=3)=[C:43]([NH:45][C:46](=[O:48])[CH3:47])[N:44]=2)[N:41]=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:36]2[CH:37]=[CH:38][C:39]3[N:40]([C:42]([C:49]4[CH:54]=[CH:53][N:52]=[CH:51][CH:50]=4)=[C:43]([NH:45][C:46](=[O:48])[CH3:47])[N:44]=3)[N:41]=2)=[CH:6][C:7]=1[NH:8][S:9]([C:12]1[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=1)(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 53363355n-[2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-4-fluorobenzene-1-sulfonamideHCID 86631966HCID 86631966, compound

Product 1

HCID 44124988HCID 44124988, compoundYield 26.2%

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)-4-fluorobenzenesulfonamide (81 mg, 196 μmol), N-(6-chloro-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide-TFA salt (47.0 mg, 163 μmol), sodium carbonate (69 mg, 653 μmol) and dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) (9.1 mg, 16 μmol). The vial was sealed with a septum cap and 1,4-dioxane (2 mL) and water (0.2 mL) were added under positive N2 flow. The mixture was sparged for 10 min with N2 and 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 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 the title compound, N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (23 mg, 26% yield) as a yellow solid. LCMS (ESI positive ionization) m/z: 538.0 (M+1); 1H NMR (400 MHz, MeOH-d6) δ ppm 2.27 (s, 3H) 7.95-8.07 (m, 2H) 8.21 (dd, J=61.57, 9.54 Hz, 2H) 8.63-8.71 (m, 3H) 8.76-8.81 (m, 2H) 8.82-8.86 (m, 2H) 8.87-8.92 (m, 2H).

Workup

  1. customThe vial was sealed with a septum
  2. customcap
  3. customThe mixture was sparged for 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-72c13d3a70d9478f9a66925526f1a7e3
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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