Potassium Fluoride → HCID 58335815, compound

HRID 1890675Notes

Reaction equation

HRID 1890675 reaction equation
[F-].[K+].[Br:3][C:4]1[N:8]2[N:9]=[C:10](Cl)[CH:11]=[CH:12][C:7]2=[N:6][CH:5]=1.[F:14][C:15]1[CH:16]=[C:17]([CH:21]2[C@@H:25]([O:26][Si](C(C)C)(C(C)C)C(C)C)[CH2:24][CH2:23][NH:22]2)[CH:18]=[CH:19][CH:20]=1>CS(C)=O.CO>[Br:3][C:4]1[N:8]2[N:9]=[C:10]([N:22]3[CH2:23][CH2:24][C@H:25]([OH:26])[CH:21]3[C:17]3[CH:18]=[CH:19][CH:20]=[C:15]([F:14])[CH:16]=3)[CH:11]=[CH:12][C:7]2=[N:6][CH:5]=1

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 128723233-Bromo-6-chloroimidazo(1,2-b)pyridazineHCID 67308441HCID 67308441, compound

Product 1

HCID 58335815HCID 58335815, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

In step 3-4, KF (100 mg, 1.72 mmol) and 3-bromo-6-chloroimidazo[1,2-b]pyridazine (12-1) (700 mg, 3.0 mmol) were added to a solution of (3S)-2-(3-fluorophenyl)-3-(triisopropylsilyloxy)pyrrolidine (4-3) (700 g, 2.0 mmol) in 3 mL of DMSO. The resulting slurry was heated to 110° C. for 6 hours and then cooled, diluted with 8 mL of MeOH and purified using reverse phase C-18 chromatography (water/acetonitrile 90:10 to 10:90 gradient) to furnish (3S)-1-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-2-(3-fluorophenyl)pyrrolidin-3-ol (3-4) as a solid (as a mixture of diastereomers). 1H NMR (400 MHz, D6 acetone) δ ppm 8.20 (app t, J=6.5 Hz, 1H), 7.85-6.70 (m, 6H), 5.05 (app d, J=5.5 Hz, 1H), 4.68 (app q, J=7.5 Hz, 1H), 4.30 (br s, 1H), 4.01-3.92 (m, 1H), 3.82-3.70 (m, 1H), 2.35-1.87 (m, 2H). LCMS observed m/z 377.1, 379.1 major ion.

Workup

  1. temperaturecooled
  2. custompurified

Sources & evidence

ORD record
ord-a456af0435cb4cc7984a5b91fbce0793
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

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