3-Bromo-6-chloroimidazo(1,2-b)pyridazine → (6-Chloroimidazo[1,2-b]pyridazin-3-yl)(1-methyl-1H-indazol-5-yl)methanol

HRID 456153Notes

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.[CH3:16][N:17]1[C:25]2[C:20](=[CH:21][C:22]([CH:26]=[O:27])=[CH:23][CH:24]=2)[CH:19]=[N:18]1>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:26]([C:22]3[CH:21]=[C:20]4[C:25](=[CH:24][CH:23]=3)[N:17]([CH3:16])[N:18]=[CH:19]4)[OH:27])=[CH:3][N:4]=2)[N:7]=1

Participants

Conditions

Temperature: -10 °C

Procedure

To a solution of 3-bromo-6-chloroimidazo[1,2-b]pyridazine (232.0 mg, 1.00 mmol) in 5 mL THF, was added ethylmagnesium bromide (1.50 mL, 1.50 mmol) at −10° C. After stirring at −10° C. for 1 hour, 1-methyl-1H-indazole-5-carbaldehyde (240.0 mg, 1.50 mmol) was added. The mixture was allowed to warm to room temperature slowly and stirred for additional 2 hours. The reaction was quenched with Sat. NH4Cl solution and concentrated under reduced pressure. The residue was diluted with water, and extracted with EtOAc twice. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was washed with DCM to give the title compound as a white solid (230 mg, 70%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.21 (d, 1H), 8.02 (s, 1H), 7.81 (s, 1H), 7.59 (d, 1H), 7.56 (s, 1H), 7.49 (d, 1H), 7.35 (d, 1H), 6.29 (d, 1H), 6.21 (d, 1H), 4.02 (s, 3H). LCMS (method A): [MH]+=314, tR=4.44 min

Workup

temperatureto warm to room temperature slowly
stirringstirred for additional 2 hours
customThe reaction was quenched with Sat. NH4Cl solution
concentrationconcentrated under reduced pressure
additionThe residue was diluted with water
extractionextracted with EtOAc twice
dry with materialdried over Na2SO4
concentrationconcentrated
washThe crude product was washed with DCM

Sources & evidence

ORD record: ord-2fc237eba18545e598001dc63119a7ea
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497368B2

Reaction notes

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