Hydrogen Peroxide → HCID 68350417, compound

HRID 877833Notes

Reaction equation

HRID 877833 reaction equation
[OH-:1].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:11]([NH:12][C@@H:13]3[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:15][C@@:14]3([F:29])[CH3:28])=[C:10]([C:30]#[N:31])[CH:9]=[N:8][N:7]2[CH:32]=1.OO>CS(C)=O.CO>[Br:3][C:4]1[CH:5]=[C:6]2[C:11]([NH:12][C@@H:13]3[CH2:17][N:16]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:15][C@@:14]3([F:29])[CH3:28])=[C:10]([C:30](=[O:1])[NH2:31])[CH:9]=[N:8][N:7]2[CH:32]=1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 68350418HCID 68350418, compound

Product 1

HCID 68350417HCID 68350417, compoundYield 92.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

A 2.0 M aqueous NaOH (0.6 mL, 1.200 mmol) was added dropwise to a solution of (3S,4R)-benzyl 4-((6-bromo-3-cyanopyrrolo[1,2-b]pyridazin-4-yl)amino)-3-fluoro-3-methylpyrrolidine-1-carboxylate (120 mg, 0.254 mmol) in methyl sulfoxide (2 mL), methanol (2 mL) and hydrogen peroxide (0.3 mL, 2.94 mmol) at 0° C. After 1 h at 0° C., the mixture was quenched with saturated NaHCO3 (5 mL), diluted with ethyl acetate (80 mL), washed with water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography, eluting with 20 to 80% ethyl acetate in hexanes, to give (3S,4R)-benzyl 4-((6-bromo-3-carbamoylpyrrolo[1,2-b]pyridazin-4-yl)amino)-3-fluoro-3-methylpyrrolidine-1-carboxylate (115 mg, 92% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 10.71 (d, J=8.4 Hz, 1H), 7.98-7.85 (m, 1H), 7.73-7.59 (m, 1H), 7.51-7.30 (m, 5H), 6.79 (d, J=7.5 Hz, 1H), 5.79-5.54 (m, 2H), 4.69-4.33 (m, 1H), 4.32-4.08 (m, 1H), 4.00-3.74 (m, 1H), 3.59-3.42 (m, 2H), 1.61-1.43 (m, 3H); MS (ES+) m/z: 490.1 (M+H).

Workup

  1. customthe mixture was quenched with saturated NaHCO3 (5 mL)
  2. additiondiluted with ethyl acetate (80 mL)
  3. washwashed with water, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 20 to 80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-df6eb8c0c5eb42f183b704f3109bf250
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

Loading…