Potassium Fluoride → 3-Bromo-6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

HRID 1890677Notes

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.[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=1[CH:22]1[CH2:26][CH2:25][CH2:24][NH:23]1>CS(C)=O>[Br:3][C:4]1[N:8]2[N:9]=[C:10]([N:23]3[CH2:24][CH2:25][CH2:26][CH:22]3[C:16]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:15]=3[CH3:14])[CH:11]=[CH:12][C:7]2=[N:6][CH:5]=1

Participants

Conditions

Temperature: 130 °C

Procedure

In step 4-1, potassium fluoride (58 mg, 1.0 mmol), and (3-bromo-6-chloroimidazo[1,2-b]pyridazine (12-1) (100 mg, 0.43 mmol) was added to a solution of 2-(2,5-dimethylphenyl)pyrrolidine (100 mg, 0.57 mmol) in 3 mL of DMSO. The reaction mixture was heated to 130° C. and stirred for 6 hours at 130° C. The reaction mixture was cooled to room temperature and purified using normal phase flash chromatography with ethyl acetate and hexanes (1:1) as a mobile phase to yield 3-bromo-6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (4-1) as its racemic mixture. 1H NMR (400 MHz, D3 acetonitrile) δ ppm 7.50 (app d, J=9.5 Hz, 1H), 7.40 (br s, 1H), 7.08 (d, J=6.5 Hz, 1H), 6.92 (d, J=6.6 Hz, 1H), 6.82 (br s, 1H), 6.58 (br d, J=9.5 Hz, 1H), 5.28 (br d, J=5.0 Hz, 1H), 4.08-3.95 (m, 1H), 3.62 (app q, J=6.4 Hz, 1H), 3.30 (s, 1H), 2.51-2.42 (m, 1H), 2.24 (br s, 6H), 2.17-2.04 (m, 2H). LCMS observed m/z 371.1, 373.1 major ion.

Workup

temperatureThe reaction mixture was cooled to room temperature
custompurified

Sources & evidence

ORD record: ord-abca0b07d3414fa38fa01d57caccdb1c
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507488B2

Reaction notes

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