Trimethylsilyl iodide → 6-bromo-4-(((3S,4S)-4-(fluoromethyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877799Notes

Reaction equation

HRID 877799 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([CH2:16][F:17])[CH2:14][N:13](C(OCC4C=CC=CC=4)=O)[CH2:12]3)=[C:8]([C:28](=[O:30])[NH2:29])[CH:7]=[N:6][N:5]2[CH:31]=1.[Si](I)(C)(C)C>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@H:11]3[C@@H:15]([CH2:16][F:17])[CH2:14][NH:13][CH2:12]3)=[C:8]([C:28]([NH2:29])=[O:30])[CH:7]=[N:6][N:5]2[CH:31]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 86707902(3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylate

Product 1

HCID 682911116-bromo-4-(((3S,4S)-4-(fluoromethyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 128.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (3S,4S)-benzyl 3-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-(fluoromethyl)pyrrolidine-1-carboxylate (1.15 g, 2.345 mmol) in Acetonitrile (15 mL) at 0° C. was added TMS-I (1.277 mL, 9.38 mmol) dropwise and the resulting mixture was stirred for 10 min. and then allowed to warm to RT and stir for 1 hr. The reaction was quenched with 1.5 mL of MeOH and stirred for 10 minutes. The solid was collected as a hydroiodide salt of the title compound (1.07 g, 94% yield). MS (ES+) m/z: 356.1, 358.0 (M+H); HPLC: 96.7%, retention time: 1.525 min (analytical HPLC Method H).

Workup

  1. stirringstir for 1 hr
  2. customThe reaction was quenched with 1.5 mL of MeOH
  3. stirringstirred for 10 minutes

Sources & evidence

ORD record
ord-bdaf7b84f25249a2810527a8e2cb7b55
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…