With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.486-73-7,Isoquinoline-1-carboxylic acid,as a common compound, the synthetic route is as follows.
General procedure: At 0C, to a solution of 1.0 mmol of isoquinoline- 1 -carboxylic acid in anhydrous THF(20mL),0.135g(1.0mmol) of HOBt and 1.0 mmol of (2S,3R)- 2-Amino-3-hydroxy-N-octylbutanamide, (2S,3R)-2-Amino-3-hydroxy-N- dodecylbutanamide, (2S,3R)-2-Amino-3-hydroxy-N-tetradecylbutanamide, or (2S,3R)-2-Amino-3-hydroxy-N-octadecylbutanamide were added. After 5 min, 0.220g (1.1 mmol) of EDOHC1 was added, and the pH of the solution was adjusted to 8-9 with 4-methylmorpholine. The mixture was stirred at 0 C for 2 h and at room temperature overnight. On evaporation the residue was dissolved in 80 mL of ethyl acetate. The solution was washed successively with saturated sodium bicarbonate, 5% potassium bisulfate, and saturated sodium chloride, and the organic phase was separated and dried over anhydrous magnesium sulfate for 2 h. After filtration and evaporation under reduced pressure crude product was obtained and recrystallized using ethyl acetate to obtain compounds NZJUlf, NZJU2f, NZJU3f, and NZJU4f. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(octylamino)butan-2-yl)- isoquinoline- 1 -carboxamide (NZJUlf) was obtained in a yield of 0.258 g (67.0%) as colorless powder. XH NMR (300 MHz, CDC13) delta 9.51 (d, J= 8.1 Hz, 1H), 9.08 (d, J= 8.0 Hz, 1H), 8.52 (d, J= 5.5 Hz, 1H), 7.92 – 7.79 (m, 2H), 7.79 – 7.61 (m, 2H), 6.89 (s, 1H), 4.66 – 4.46 (m, 2H), 3.32 – 3.1 1 (m, 2H), 1.56 – 1.42 (m, 2H), 1.34 – 1.04 (m, 13H), 0.82 (t, J= 6.7 Hz, 3H); 13C NMR (75 MHz, CDC13) delta 171.4, 167.5 , 147.2, 140.6, 137.5, 130.6, 128.8, 127.3, 127.0, 124.8 , 66.6, 56.9, 39.6, 31.7, 29.4, 29.2, 26.9, 22.6, 18.6, 14.1; ESI/MS (m/e) 386.20 [M+H]+; Anal. Calcd. For C22H31N3O3: C, 68.54; H, 8.1 1; N, 10.90%. Found: C, 68.47; H, 8.24; N, 10.86%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(dodecylamino)butan-2-yl)- isoquinoline- 1 -carboxamide (NZJU2f) was obtained in a yield of 0.310 g (70.3%) as colorless powder. XH NMR (300 MHz, CDC13) delta 9.51 (d, J= 7.6 Hz, 1H), 9.08 (d, J= 7.8 Hz, 1H), 8.52 (d, J= 5.2 Hz, 1H), 7.95 – 7.80 (m, 2H), 7.80 – 7.62 (m, 2H), 6.89 (s, 1H), 4.67 – 4.45 (m, 2H), 3.35 – 3.09 (m, 2H), 1.57 – 1.41 (m, 2H), 1.37 – 0.98 (m, 21H), 0.87 (t, J= 6.4 Hz, 3H); 13C NMR (75 MHz, CDC13) delta 171.4, 167.3 , 147.3, 140.6, 137.4, 130.5, 128.8, 127.3, 127.0, 124.7, 66.6, 56.9, 39.6, 31.9, 29.6, 29.5, 29.4, 29.3, 26.9, 22.7, 18.6, 14.1; ESI/MS (m/e) 442 [M+H]+; Anal. Calcd. For C26H39N303: C, 70.71; H, 8.90; N, 9.52%. Found: C, 70.68; H, 8.86; N, 9.49%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(tetradecylamino)butan-2-yl)- isoquinoline-1 -carboxamide (NZJU3f) was obtained in a yield of 0.317 g (67.6%) as colorless powder. XH NMR (300 MHz, CDC13) delta 9.51 (d, J= 8.3 Hz, 1H), 9.07 (d, J= 8.1 Hz, 1H), 8.52 (d, J= 5.5 Hz, 1H), 7.94 – 7.79 (m, 2H), 7.78 – 7.60 (m, 2H), 6.89 (s, 1H), 4.68 – 4.46 (m, 2H), 3.35 – 3.1 1 (m, 2H), 1.58 – 1.39 (m, 2H), 1.39 – 1.00 (m, 25H), 0.88 (t, J= 6.4 Hz, 3H); 13C NMR (75 MHz, CDC13) delta 171.2, 167.2 , 147.4, 140.6, 137.4, 130.5, 128.7, 127.3, 127.0, 124.7 , 66.7, 57.2, 39.6, 31.9, 29.7, 29.6, 29.4, 29.3, 28.3, 26.9, 22.7, 18.6, 14.1; ESI/MS (m/e) 470 [M+H]+; Anal. Calcd. For C28H43 3O3: C, 71.61 ; H, 9.23; N, 8.95%. Found: C, 71.58; H, 9.19; N, 8.98%. N-((2S,3R)-3-hydroxy- 1-oxo- 1 -(octadecylamino)butan-2-yl)- isoquinoline- 1 -carboxamide (NZJU4f) was obtained in a yield of 0.409 g (77.3%) as colorless powder. XH NMR (300 MHz, CDC13) delta 9.46 (d, J= 8.3 Hz, 1H), 9.08 (d, J= 7.4 Hz, 1H), 8.52 (d, J= 5.2 Hz, 1H), 7.94 – 7.83 (m, 2H), 7.81 – 7.62 (m, 2H), 6.95 (s, 1H), 4.68 – 4.47 (m, 2H), 3.37 – 3.15 (m, 2H), 1.54 – 1.40 (m, 2H), 1.38 – 1.00 (m, 33H), 0.88 (t, J= 6.2 Hz, 3H); 13C NMR (75 MHz, CDC13) delta 171.5, 167.4 , 147.4, 140.5, 137.4, 130.6, 128.8, 127.3, 127.0, 124.7, 66.7, 57.0, 39.6, 31.9, 29.7, 29.6, 29.4, 29.3, 26.9, 22.7, 18.6, 14.1; ESI/MS (m/e) 526 [M+H]+; Anal. Calcd. For C32H51N3O3: C, 73.10; H, 9.78; N, 7.99%. Found: C, 73.07; H, 9.86; N, 8.02%.
486-73-7, The synthetic route of 486-73-7 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; ZHEJIANG UNIVERSITY; GEORGIA REGENTS RESEARCH INSTITUTE, INC.; LIU, Feiyan; LIU, Kebin; HUANG, Zhizhen; WU, Ping; WO2014/66613; (2014); A2;,
Isoquinoline – Wikipedia
Isoquinoline | C9H7N – PubChem