Phosphoric Acid → 1-(2-(Tert-butoxy)pyridin-4-yl)-4-chloro-5-phenylphthalazine

Temperatur

95 °C

To a solution of 1,4-dichloro-5-phenylphthalazine (0.400 g, 1.45 mmol), 2-(tert-butoxy)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.484 g, 1.75 mmol) in dioxane (20 mL) and water (2 mL) was added phosphoric acid, potassium salt (0.617 g, 2.91 mmol). The reaction mixture was purged with nitrogen gas for 30 min and then Pd2(dba)3 (0.013 g, 0.015 mmol) was added followed by tricyclohexylphosphonium tetrafluoroborate (11 mg, 0.029 mmol). The purging was continued for a further 15 min and the reaction mixture heated to 95° C. for 12 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography using Combiflash Isco (REDISEP®, SiO2, 12 g, 0-30% ethyl acetate/petroleum ether) to get 1-(2-(tert-butoxy)pyridin-4-yl)-4-chloro-5-phenylphthalazine (0.400 g, 33.2%) as a brown solid. LCMS (Condition 11): retention time 1.22 min, [M+1]=390.2. 1H NMR (400 MHz, DMSO-d6) δ 1.70 (s, 9 H), 6.84 (br s, 1 H), 7.05 (dd, J=1.2 Hz, J=5.2 Hz, 1 H), 7.36-7.44 (m, 2 H), 7.47-7.51 (m, 3 H), 8.06 (dd, J=1.2 Hz, J=7.6 Hz, 1 H), 8.15 (dd, J=0.8 Hz, J=4.8 Hz, 1 H), 8.26 (dd, J=7.2 Hz, J=8.0 Hz, 1 H), 8.47 (d, J=1.2 Hz, J=8.4 Hz, 1 H).

1. customThe reaction mixture was purged with nitrogen gas for 30 min
2. extractionextracted with ethyl acetate (3×50 mL)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by flash chromatography

ORD-Eintrag

ord-93214ca7b7ca41e6ac298f1c052fe855

Quelldatensatz

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09242966B2