Nitrogen → 3-[1-(4,6-Difluoro-1-methyl-1H-indazol-5-yl)-ethyl]-6-(1-ethoxy-vinyl)-imidazo[1,2-b]pyridazine

HRID 456091Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[C:14]([F:24])=[C:15]4[C:19](=[CH:20][C:21]=3[F:22])[N:18]([CH3:23])[N:17]=[CH:16]4)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:30]([O:32][CH2:33][CH3:34])=[CH2:31])CCC.N#N>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C:14]1[C:13]([CH:11]([C:8]2[N:6]3[N:7]=[C:2]([C:30]([O:32][CH2:33][CH3:34])=[CH2:31])[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)[CH3:12])=[C:21]([F:22])[CH:20]=[C:19]2[C:15]=1[CH:16]=[N:17][N:18]2[CH3:23]

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of 6-chloro-3-[1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)-ethyl]-imidazo[1,2-b]pyridazine (80 mg, 0.23 mmol) and tributyl(1-ethoxyvinyl)stannane (0.234 mL, 0.69 mmol) in 15 mL DMF was purged with N2 for 30 min and then tetrakis-(triphenylphosphine)-palladium (80 mg, 0.069 mmol) was added, and the solution was heated at 95° C. for overnight. Then the reaction was quenched with water, extracted with EtOAc for three times. The organic layers were combined, washed with KF solution and brine, dried over Na2SO4. Solvent was evaporated and the crude product (80 mg, 90%) was used in the next step without further purification. LCMS (method C): [MH]+=384.0, tR=4.67 min

Workup

customThen the reaction was quenched with water
extractionextracted with EtOAc for three times
washwashed with KF solution and brine
dry with materialdried over Na2SO4
customSolvent was evaporated
customthe crude product (80 mg, 90%) was used in the next step without further purification

Sources & evidence

ORD record: ord-482c62a2afc94bf0b9ddb4565f831fa6
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497368B2

Reaction notes

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