Trifluoroacetic acid → 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877753Notes

Reaction equation

HRID 877753 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][C@H:12]3[CH2:24][CH3:25])=[C:8]([C:26](=[O:28])[NH2:27])[CH:7]=[N:6][N:5]2[CH:29]=1.FC(F)(F)C(O)=O>ClCCl>[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[CH2:24][CH3:25])=[C:8]([C:26]([NH2:27])=[O:28])[CH:7]=[N:6][N:5]2[CH:29]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68291228HCID 68291228, compound

Product 1

HCID 682916696-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3R,4R)-tert-butyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3-ethylpiperidine-1-carboxylate (350 mg, 0.750 mmol) in dichloromethane (3.8 ml) cooled to 0° C. was added trifluoroacetic acid (578 μl, 7.50 mmol). The reaction was allowed to warm to room temperature and stirring was continued for 1 hr. After removal of the solvent, the residue was taken into ethyl acetate, washed successively with saturated sodium bicarbonate, water, and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure, yielding 6-bromo-4-(((3R,4R)-3-ethylpiperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (275 mg, 0.75 mmol, 100% yield) as a yellow solid. LCMS (Method K) m/z 368.3 ([M+H]+). Analytical SFC conditions, Column: CC4 from ES Industries; Mobile phase: 10-50% MeOH (with 0.1% DEA) in CO2 in 8 min, 50% MeOH (with 0.1% DEA) in CO2 for 4 more min; Temperature: 40° C., Flow rate: 3 mL/min, BPR: 140 bars, Detection: UV (254 & 220 nm). Retention Time (min): 8.153 (>98.5% ee).

Workup

  1. customAfter removal of the solvent
  2. washwashed successively with saturated sodium bicarbonate, water, and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-76cd9a58fabe4fb19c793608cc77fc3d
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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