Cesium carbonate → 3-Chloro-4-methyl-6-phenylpyridazine

温度

80 °C

3,6-Dichloro-4-methylpyridazine (1.00 g, 6.1 mmol) was mostly dissolved in dioxane (22.5 mL) then added phenylboronic acid (0.82 g, 6.7 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.25 g, 0.31 mmol) and a solution of cesium carbonate (6.0 g, 18 mmol) in water (7.5 mL). The reaction mixture was heated at 80° C. for 6 hours. The reaction mixture was concentrated under vacuum and the remaining solid was triturated with water. The solid was collected on a glass frit, washing well with water. The sample was purified by flash chromatography eluting with 1:4 ethyl acetate/hexane to afford 3-chloro-4-methyl-6-phenylpyridazine as an off-white solid. MS (ESI pos. ion) m/z: 205.2 (MH+). Step 2. 3-Chloro-4-methyl-6-phenylpyridazine (0.510 g, 2.49 mmol) was dissolved in hydrazine (1.56 ml, 49.8 mmol) then the reaction mixture was heated at 100° C. for 1.5 hours. The precipitate that had formed in the mixture was collected and washed with iPrOH. The solid was dried under high vacuum to afford 1-(4-methyl-6-phenylpyridazin-3-yl)hydrazine as a pale yellow solid. MS (ESI pos. ion) m/z: 201.1 (MH+). The remaining synthesis of 7-methoxy-N-((8-methyl-6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine was conducted as described in general Method B.

1. concentrationThe reaction mixture was concentrated under vacuum
2. customthe remaining solid was triturated with water
3. customThe solid was collected on a glass frit
4. washwashing well with water
5. customThe sample was purified by flash chromatography
6. washeluting with 1:4 ethyl acetate/hexane

ORDレコード

ord-dc76c7f48b6f44e18fe60431ec6daacd

出典データセット

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08198448B2