The Synthesis of 5-Oxoperhydroisoquinolines

On the Way to Selective PARP‐2 Inhibitors. Design, Synthesis, and Preliminary Evaluation of a Series of Isoquinolinone Derivatives

“…5‐Benzoyloxyisoquinolin‐1(2 H )‐one (54): Following general procedure B starting from 5‐hydroxyisoquinolin‐1(2 H )‐one ( 5 )20 (0.1 g, 0.62 mmol) and benzoyl chloride (0.11 g, 0.09 mL, 0.74 mmol), the title compound 54 was obtained as a pure solid (0.04 g, 24.3 %); mp: 233–235 °C; 1 H NMR ([D 6 ]DMSO, 400 MHz): δ =6.39 (d, J =7.2 Hz, 1 H,), 7.19 (t, J =6 Hz, 1 H,), 7.55 (t, J =7.9 Hz, 1 H), 7.63–7.69 ( m, 3 H), 7.79 (t, J =7.4 Hz, 1 H), 8.14 (d, J =8 Hz, 1 H), 8.21 (dd, J =1.4 and 7.1 Hz, 2 H), 11.43 ppm (bs, 1 H); 13 C NMR ([D 6 ]DMSO, 100.6 MHz): δ =99.69, 126.63, 127.53, 128.29, 129.32, 130.20, 131.04, 131.82, 132.10, 133.10, 136.27, 147.28, 163.04, 166.39 ppm; anal. calcd for C 16 H 11 NO 3 : C 72.45 %, H 4.18 %, N 5.28 %, found: C 72.31 %, H 3.98 %, N 5.02 %.…”

“…5‐hydroxy‐3,4‐dihydroisoquinolin‐1(2 H )‐one ( 4 )18 was prepared by starting from the commercially available 4‐hydroxyindan‐1‐one ( 10 ) via a modified Smith rearrangement optimized to obtain the desired regioisomer 4 in 57 % yield, with a 7:3 ratio with respect to 11 19 (Scheme ). The 5‐hydroxyisoquinolin‐1(2 H )‐one ( 5 )20 was obtained in 34 % yield from 5‐isoquinoline sulfonic acid ( 12 ) by submitting 12 to alkaline fusion20 (Scheme ).…”

Synthetic Pathways to 2,2-Dimethyl-6-oxo-1-cyclohexaneacetic Acid, a Useful Isoprenoid Building Block

“…Furthermore, the experimental conditions and workup are simple and suited for large-scale preparation. The first synthetic route to 1 involved the reaction of 12 with phosphorus oxychloride to give a chloro derivative 13 followed by a conjugate addition of lithium dimethylcuprate with 13 and then hydrolysis of the resultant keto ester 15 (method A). Two additional routes utilized diketo acid 14 9 derived from 12 .…”

Hydrogenation of Substituted Isoquinolines over Nickel Catalyst I: The Effects of Pressure and Temperature on the Hydrogenation of 5-Nitro-2-alkylisoquinolinium Salts

“…While the use of Raney nickel catalyst as a hightemperature/high-pressure hydrogenation catalyst is not new (6), its application in a one-stage reduction of substituted isoquinolines to their fully saturated analogs has received little attention (7). The numerous attempts (8) to reproduce the reductive alkylation experiments of Georgian et al (7) prompted a more detailed study of the reduction of isoquinolines using nickel catalyst. The hydrogenation of 5-nitro-2-methylisoquinoliniuni p-toluenesulfonate has been studied at various high temperatures and pressures.…”

“…Since their work had also demonstrated significant pharmacological differences between stereoisomers of some derivatives of these 5-aminodecahydroisoquinolines (2) the authors decided to investigate a one-stage high-pressure/hightemperature hydrogenation of a 5-nitroisoquinolinium salt over Raney nickel catalyst to determine the effects of temperature and pressure on both the yield and isomer content of the product. While the use of Raney nickel catalyst as a hightemperature/high-pressure hydrogenation catalyst is not new (6), its application in a one-stage reduction of substituted isoquinolines to their fully saturated analogs has received little attention (7). The numerous attempts (8) to reproduce the reductive alkylation experiments of Georgian et al (7) prompted a more detailed study of the reduction of isoquinolines using nickel catalyst.…”