1,2-Dimethoxyethane → HCID 178448784, compound

HRID 870656Notes

Reaction equation

[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12](B(O)O)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].Br[C:19]1[N:20]=[CH:21][NH:22][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:19]3[N:20]=[CH:21][NH:22][CH:23]=3)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of (6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acid (120 mg, 0.5 mmol), 4-bromo-1H-imidazole (75 mg, 0.5 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (40 mg, 0.050 mmol), potassium phosphate (210 mg, 1.0 mmol), DME (1.5 mL) and H2O (0.5 mL) was heated in a sealed conical vessel at 140° C. for 600 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-imidazol-4-yl)-imidazo[1,2-b]pyridazin-6-yl]-amine (95 mg, 72%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.99 (br. s., 1H), 7.82 (d, J=1.0 Hz, 2H), 7.60 (d, J=9.6 Hz, 1H), 6.68 (d, J=9.6 Hz, 1H), 3.44 (t, J=7.1 Hz, 2H), 1.69-1.82 (m, 2H), 1.46-1.60 (m, 2H), 1.03 (t, J=7.3 Hz, 3H); LCMS (ESI) m/e 257.2 [(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-35c40b5b363640608f30e790e061fbe2
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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