Potassium Phosphate, Tribasic → (1-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1H-pyrazol-4-yl)methanol

Temperatur

100 °C

To a microwave vial was added (1-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazol-4-yl)methanol (87 mg, 0.26 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine Intermediate 1-1 (74.5 mg, 0.26 mmol), potassium phosphate (168 mg, 0.79 mmol), Pd2(dba)3 (12.06 mg, 0.01 mmol), and SPhos (10.82 mg, 0.03 mmol), followed by addition of 1,4-dioxane (5 mL)/H2O (1 mL). The vial was purged with N2 for 10 min and the reaction mixture was heated at 100° C. in the microwave for one hour. The reaction mixture was concentrated in vacuo. The crude material was adjusted to pH 3 using 1 M HCl aqueous solution and loaded on an SCX column. The crude material was washed with methanol then eluted with 2 N ammonia in methanol. The product-containing fractions were concentrated to afford (1-(3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl)-1H-pyrazol-4-yl)methanol (100 mg, MS: 451.4 [M+H+].).

1. customThe vial was purged with N2 for 10 min
2. concentrationThe reaction mixture was concentrated in vacuo
3. washThe crude material was washed with methanol
4. washthen eluted with 2 N ammonia in methanol
5. concentrationThe product-containing fractions were concentrated

ORD-Eintrag

ord-24442f437295413585fc5f01e1e4fd61

Quelldatensatz

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08729263B2