Ethyl Acetate → 3-(4-methoxy-benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine

HRID 69157Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)=[CH:9][N:10]=2)[N:7]=1.C([O-])([O-])=O.[Na+].[Na+].CCO[C:29]([CH3:31])=O>[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>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][C:8]2[N:6]3[N:7]=[C:2]([C:29]4[CH:31]=[N:7][N:6]([CH3:8])[CH:5]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 180 °C

Procedure

The compound 6-chloro-3-(4-methoxy-benzyl)-imidazo-[1,2-b]-pyridazine (Stage 4.1, 100 mg, 0.36 mmol) was introduced in a microwave reactor with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)-1H-pyrazole (75 mg, 0.36 mmol) and dissolved in 1 mL of 2-dimethoxyethane. An aqueous solution of 2 M Na2CO3 (660 μL, 1.3 mmol) was added to this mixture and also tetrakis-(triphenylphosphine)-palladium (21 mg, 0.02 mmol). The RM was heated at 180° C. for 30 min under microwave irradiations. The reaction was taken up with EtOAc and washed with 10% Na2CO3 and brine. The organic layer was dried over Na2SO4 and the solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The white solid the title compound was obtained (tR 1.0 min (conditions 2), MH+=320).

Workup

washwashed with 10% Na2CO3 and brine
dry with materialThe organic layer was dried over Na2SO4
customthe solvent was removed
customThe residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)

Sources & evidence

ORD record: ord-66a8e8987746410c9ec2f216fa44426c
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822468B2

Reaction notes

Loading…