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

HRID 877824Notes

Reaction equation

HRID 877824 reaction equation
I.[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][NH:14][CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1.C(N(CC)C(C)C)(C)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl>[Br:2][C:3]1[CH:4]=[C:5]2[C:10]([NH:11][C@H:12]3[C@@H:16]([O:17][CH3:18])[CH2:15][N:14]([S:33]([CH3:32])(=[O:35])=[O:34])[CH2:13]3)=[C:9]([C:19]([NH2:21])=[O:20])[CH:8]=[N:7][N:6]2[CH:22]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 682919346-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide

Product 1

HCID 682910436-bromo-4-(((3R,4S)-4-methoxy-1-(methylsulfonyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 6-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (from Step 2 of Example 202, 210 mg, 0.436 mmol) in dichloromethane (2 mL), was added N,N-diisopropylethylamine (0.23 mL, 1.31 mmol) and methanesulfonyl chloride (0.043 mL, 0.52 mmol) at rt. The mixture was stirred at rt for 2 h. The reaction was then quenched with water, diluted with dichloromethane, washed with aq. sodium bicarbonate and brine. The organic layer was dried and concentrated. The crude was tritrated in ether and filtered to give 6-bromo-4-(((3R,4S)-4-methoxy-1-(methylsulfonyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (136 mg, 72% yield) as a yellow solid. MS (ES+) m/z: 432.3, 463.1 (M+H); LC retention time: 2.31 min (analytical HPLC Method H).

Workup

  1. customThe reaction was then quenched with water
  2. additiondiluted with dichloromethane
  3. washwashed with aq. sodium bicarbonate and brine
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. filtrationfiltered

Sources & evidence

ORD record
ord-c606d0b62c5842ceae2c705609073448
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…