3-Bromo-6-chloroimidazo(1,2-b)pyridazine → (6-Chloroimidazo[1,2-b]pyridazin-3-yl)(7-fluoroquinolin-6-yl)methanol

HRID 69217

Reaction equation

Br[C:2]1[N:6]2[N:7]=[C:8]([Cl:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.C([Mg]Br)C.[F:16][C:17]1[CH:26]=[C:25]2[C:20]([CH:21]=[CH:22][CH:23]=[N:24]2)=[CH:19][C:18]=1[CH:27]=[O:28]>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:27]([C:18]3[CH:19]=[C:20]4[C:25](=[CH:26][C:17]=3[F:16])[N:24]=[CH:23][CH:22]=[CH:21]4)[OH:28])=[CH:3][N:4]=2)[N:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

3-Bromo-6-chloro-imidazo[1,2-b]pyridazine (1.327 g, 5.71 mmol) was dissolved THF (40 mL) and under nitrogen conditions, it was cooled down to 0° C. and ethylmagnesium bromide solution (1 M, 6.85 mL) was added. The RM was stirred at rt for 30 min then a solution of 7-fluoro-quinoline-6-carbaldehyde (Intermediate B), (1.0 g, 5.71 mmol) in THF (20 mL) was added by 0° C. The RM was stirred at rt for 2 h. The solvent was partially removed by evaporation and water (40 mL) was added to the residual mash. After 1 h stirring, the crystallized product was filtered and dried overnight under vacuum to afford the title compound as a powder (tR 3.70 min (conditions 3), MH+=329, 1H-NMR in DMSO-d6: 8.90 (dd, 1H); 8.46 (d, 1H); 8.29-8.23 (m, 2H); 7.72 (d, 1H); 7.54-7.49 (m, 2H); 7.40 (d, 1H); 6.56-6.49 (m, 2H)).

Workup

stirringThe RM was stirred at rt for 2 h
customThe solvent was partially removed by evaporation and water (40 mL)
additionwas added to the residual mash
stirringAfter 1 h stirring
filtrationthe crystallized product was filtered
customdried overnight under vacuum

Sources & evidence

ORD record: ord-3d100510606d450e9beed1f95e23cb18
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822468B2

Linked notes

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