Methanesulfonyl chloride → 6-bromo-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877756Notes

Reaction equation

HRID 877756 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:16][CH2:15][NH:14][CH2:13][C@H:12]3[CH2:17][CH3:18])=[C:8]([C:19]([NH2:21])=[O:20])[CH:7]=[N:6][N:5]2[CH:22]=1.CCN(C(C)C)C(C)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:16][CH2:15][N:14]([S:33]([CH3:32])(=[O:35])=[O:34])[CH2:13][C@H:12]3[CH2:17][CH3:18])=[C:8]([C:19]([NH2:21])=[O:20])[CH:7]=[N:6][N:5]2[CH:22]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 682916696-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 682911046-bromo-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 2 of Example 125 (150 mg, 0.410 mmol) and DIEA (429 μl, 2.457 mmol) in DMF (2.7 ml) was added methanesulfonyl chloride (47.5 μl, 0.614 mmol). The reaction was stirred at room temperature for 2 hrs. After removal of the solvent, the residue was dissolved in ethyl acetate, washed successively with saturated ammonium chloride, water, and brine; dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution) to yield 6-bromo-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (95 mg, 0.214 mmol, 52.2% yield) as a yellow solid. LCMS (Method K) m/z 446.0 ([M+H]+).

Workup

  1. customAfter removal of the solvent
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed successively with saturated ammonium chloride, water, and brine
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified via medium pressure chromatography (silica gel column, EtOAc/hexanes eluent, 0-100% gradient elution)

Sources & evidence

ORD record
ord-4a482b32d870455f9c11fd32d9626c88
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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