Potassium Phosphate, Tribasic → N-(tert-butyl)-5-(4-chloro-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide

온도

95 °C

To a solution of 1,4-dichloro-5-phenylphthalazine (0.400 g, 1.45 mmol) and N-(tert-butyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.742 g, 2.18 mmol) (Johnson et al., WO 2011/28741) in 1,4-dioxane (15 mL) and water (3 mL) was added K3PO4 (0.617 g, 2.91 mmol) and the contents purged with nitrogen for 10 min. Tricyclohexylphosphine (10.2 mg, 0.0360 mmol) was added followed by Pd2(dba)3 (0.0130 g, 0.0150 mmol) and heated at 95° C. for 12 h. The reaction mixture was allowed to cool to ambient temperature. The reaction mixture was diluted with HCOONH4 buffer (pH˜5) solution and extracted with EtOAc (3×75 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by combiflash (REDISEP®, silica gel, 12 g, 30% EtOAc/hexanes) to obtain N-(tert-butyl)-5-(4-chloro-5-phenylphthalazin-1-yl)pyridine-3-sulfonamide (0.500 g, 76.0%) as a pale yellow solid. LCMS (Condition 11): retention time 1.04 min, [M+1]=453.2. 1H NMR (400 MHz, DMSO-d6) δ 1.20 (s, 9 H), 7.43-7.46 (m, 2 H), 7.50-7.54 (m, 3 H), 7.98 (s, 1 H), 7.99 (dd, J=1.2 Hz, J=8.0 Hz, 1H), 8.03 (dd, J=1.2 Hz, J=7.2 Hz, 1 H), 8.15 (dd, J=7.2 Hz, J=8.0 Hz, 1 H), 8.58 (t, J=2.0 Hz, 1 H), 9.17 (d, J=2.0 Hz, 1 H), 9.23 (d, J=2.0 Hz, 1 H).

1. customthe contents purged with nitrogen for 10 min
2. temperatureto cool to ambient temperature
3. extractionextracted with EtOAc (3×75 mL)
4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by combiflash (REDISEP®, silica gel, 12 g, 30% EtOAc/hexanes)

ORD 기록

ord-8fe2ec71ce164915917a24db71f61151

출처 데이터셋

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09242966B2