Methanesulfonyl chloride → 6-bromo-4-((3S,4S)-4-methyl-1-(methylsulfonyl)pyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877773Notes

Reaction equation

HRID 877773 reaction equation
I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH3:17])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:18]([NH2:20])=[O:19])[CH:8]=[N:7][N:6]2[CH:21]=1.CCN(C(C)C)C(C)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl.O>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([CH3:17])[CH2:15][N:14]([S:32]([CH3:31])(=[O:34])=[O:33])[CH2:13]3)=[C:9]([C:18]([NH2:20])=[O:19])[CH:8]=[N:7][N:6]2[CH:21]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 682912146-bromo-4-(((3S,4S)-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide

Product 1

HCID 682916916-bromo-4-((3S,4S)-4-methyl-1-(methylsulfonyl)pyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 85.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a slurry of 6-bromo-4-((3S,4S)-4-methylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide salt from Step 1 of Example 158 (500 mg, 1.073 mmol) and DIPEA (0.562 mL, 3.22 mmol) in DCM (5 mL) at 0° C. was added a solution of methanesulfonyl chloride (160 mg, 1.395 mmol) in 1 mL of DCM dropwise and the resulting mixture was stirred at rt for 1 h. The reaction was quenched by addition of MeOH (˜1 mL) and was then concentrated to afford a solid which was suspended in water, stirred for 30 min. and collected by vacuum filtration and dried under vacuum to afford 380 mg (85%) of the title compound. HPLC (method B) retention time 2.75 min. LCMS (m+1)=416/418 (1:1).

Workup

  1. customThe reaction was quenched by addition of MeOH (˜1 mL)
  2. concentrationwas then concentrated
  3. customto afford a solid which
  4. stirringstirred for 30 min.
  5. filtrationcollected by vacuum filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-af6ec12e63124028aa115a80a3f8942b
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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