Ethyl Acetate → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

HRID 1921608Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.C([O-])([O-])=O.[Na+].[Na+].O1[CH2:27][CH2:26]OCC1.CCOC(C)=O.[Cl-:34].[Na+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:34][C:1]1[N:2]=[N:3][C:4]([C:5]2[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=2)=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A flask was charged with 3,6-dichloropyridzine (Aldrich, 297 mg, 2.0 mmol), 1-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (499 mg, 2.4 mmol), 2 M Na2CO3 (4 mL) and dioxane (4 mL). Argon was bubbled through the reaction for 60 seconds followed by the addition of Tetrakis(triphenylphosphine)palladium (0) (231 mg, 0.2 mmol). The reaction was heated to 80° C. overnight followed by aqueous work up using EtOAc and brine. The organic layer was dried (MgSO4) and concentrated in vacuo followed by column chromatography purification (20% Ethyl Acetate in Hexanes) resulting in the title compound as a white solid (183 mg, 47%). 1H-NMR (CD3OD): δ 8.23 (1H, s), 8.08 (1H, s), 7.84 (1H, br s), 7.34 (1H, br s), 4.00 (3H, s).

Workup

customArgon was bubbled through the reaction for 60 seconds
dry with materialThe organic layer was dried (MgSO4)
concentrationconcentrated in vacuo
customfollowed by column chromatography purification (20% Ethyl Acetate in Hexanes)

Sources & evidence

ORD record: ord-9094496d0f9d45219387845bd32716e2
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173654B2

Reaction notes

Loading…