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1,2-Dimethoxyethane → HCID 178448784, compound

HRID 870656
Notes
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Reaction equation

HRID 870656 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 86696352(6-(Butylamino)imidazo[1,2-b]pyridazin-3-yl)boronic acidHCID 178418934HCID 178418934, compound

Product 1

HCID 178448784HCID 178448784, compoundYield 74.1%

Reagents, catalysts & solvents 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Catalyst
HCID 962WaterSolvent

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

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2 mL)
  3. concentrationThe combined organic layers were concentrated under reduced pressure
  4. customto afford an oil that
  5. 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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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes