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

HRID 1959662Notes

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.[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][C:18]([CH:22]=[O:23])=[CH:19][CH:20]=2)[CH:15]=[N:14]1>C1COCC1>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([CH:22]([C:18]3[CH:17]=[C:16]4[C:21](=[CH:20][CH:19]=3)[N:13]([CH3:12])[N:14]=[CH:15]4)[OH:23])=[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 THF (5 mL) was added EtMaBr (1M in THF, 1.50 mL, 1.50 mmol) at −10° C. After stirring at −10° C. for 1 h, 1-methyl-1H-indazole-5-carbaldehyde (240.0 mg, 1.50 mmol) was added. The mixture was allowed to warm to it slowly and stirred for 2 h. The reaction was quenched with saturated 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 it slowly
stirringstirred for 2 h
customThe reaction was quenched with saturated 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-8f7ad97a6a744db2a42505e13ec6f9b9
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410264B2

Reaction notes

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