Dimethyl Sulfoxide → HCID 44125612, compound

HRID 1162452Notes

Reaction equation

HRID 1162452 reaction equation
ClC1N=CC(C2C=CC3N(C=C(NC(=O)C)N=3)N=2)=CC=1NS(C)(=O)=O.Cl[C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[C:34]([NH:36][C:37](=[O:39])[CH3:38])[N:35]=2)[N:32]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CS(C)=O.C([O-])(=O)C.[K+].Br[C:68]1[CH:69]=[C:70]([O:76][CH3:77])[C:71]([O:74][CH3:75])=[N:72][CH:73]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:77][O:76][C:70]1[CH:69]=[C:68]([C:27]2[CH:28]=[CH:29][C:30]3[N:31]([CH:33]=[C:34]([NH:36][C:37](=[O:39])[CH3:38])[N:35]=3)[N:32]=2)[CH:73]=[N:72][C:71]=1[O:74][CH3:75]

Participants

9

Reactant 7

HCID 679Dimethyl SulfoxideHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 125630845-Bromo-2,3-dimethoxypyridineHCID 44125613N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamideHCID 59519510N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44125612HCID 44125612, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

Following the procedure described for N-(6-(6-chloro-5-(methylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (Example 19), N-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetamide (0.132 g, 0.627 mmol) was reacted with bis(pinacolato)diboron (0.207 g, 0.815 mmol), DMSO (6.00 mL, 84.5 mmol) and potassium acetate (0.246 g, 2.51 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.050 g, 0.062 mmol, Strem Chemical, Inc., Newburyport, Mass.) for 6 h. This was followed by treatment with 5-bromo-2,3-dimethoxypyridine (0.136 g, 0.624 mmol), aq sodium carbonate (0.312 mL, 0.624 mmol, 2 M) and trans-dichlorobis(triphenylphosphine)palladium(II) (0.0438 g, 0.0624 mmol, Strem). Purification by preparative HPLC (Phenomenex Gemini 5 micron (Phenomenex, Torrance, Calif.), C18, 100×30 mm, 5 to 65% CH3CN(0.1% TFA)/H2O(0.1% TFA) over 20 min then 100% CH3CN(0.1% TFA) for 3 minutes at 20 mL/min) followed by conversion to the free base by loading the purified material onto a 1000 mg SCX (cation exchange resin, Radleys Discovery Technology, Essex, UK) cartridge and elution with MeOH(2M NH3)/CH2Cl2 which, after concentration, afforded the title compound (0.0318 g, 16%) as a yellow solid. MS (ESI, positive ion) m/z: 314 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.11 (s, 3H), 3.92 (s, 3H), 3.95 (s, 3H), 7.83 (d, J=9.6 Hz, 1H), 7.87 (d, J=2.0 Hz, 1H), 8.05 (d, J=9.6 Hz, 1H), 8.29 (s, 1H), 8.41 (d, J=2.0 Hz, 1H), 10.89 (s, 1H).

Workup

  1. customPurification by preparative HPLC (Phenomenex Gemini 5 micron (Phenomenex, Torrance, Calif.)
  2. wait100% CH3CN(0.1% TFA) for 3 minutes at 20 mL/min) followed by conversion to the free base
  3. washonto a 1000 mg SCX (cation exchange resin, Radleys Discovery Technology, Essex, UK) cartridge and elution with MeOH(2M NH3)/CH2Cl2 which
  4. concentrationafter concentration

Sources & evidence

ORD record
ord-ebe2960fad2e496aa2ad171f44901918
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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