Acetonitrile → butyl-[3-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine

HRID 870642Notes

Reaction equation

Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[NH:16]1[CH:20]=[C:19](B(O)O)[CH:18]=[N:17]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(#N)C>Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:19]3[CH:20]=[N:16][NH:17][CH:18]=3)=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (100 mg, 0.37 mmol), (1H-pyrazol-4-yl)boronic acid (90 mg, 0.45 mmol), dichloro-bis(triphenylphosphino) palladium (II) (15 mg, 0.021 mmol), potassium phosphate (80 mg, 0.56 mmol), acetonitrile (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 160° C. for 1000 s by microwave irradiation. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 mL). The combined organic layers were concentrated under reduced pressure to afford an oil that was purified by reverse phase HPLC to afford butyl-[3-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine (60 mg, 62%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67 (s, 1H), 7.59 (d, J=9.6 Hz, 1H), 6.67 (d, J=9.6 Hz, 1H), 3.44 (t, J=7.1 Hz, 1H), 1.70-1.80 (m, 1H), 1.46-1.59 (m, 1H), 1.03 (t, J=7.3 Hz, 1H); LCMS (ESI) m/e 257.3 [(M+H)+, calcd for C13H17N6 257.1].

Workup

customThe organic layer was separated
extractionthe aqueous layer was extracted with ethyl acetate (2 mL)
concentrationThe combined organic layers were concentrated under reduced pressure
customto afford an oil that
customwas purified by reverse phase HPLC

Sources & evidence

ORD record: ord-fc5fa78766ee41edb5c063fc66ae3d99
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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