ISOQUINOLINE-5-CARBOXYLIC ACID

Isoquinoline-5-carbonitrile (6 g, 38.62 mmol) obtained in Step (1) above and distilled water (90 mL) were mixed and stirred. Isoquinoline-5-carbonitrile (6 g, 38.62 mmol) obtained in Step (1) above and distilled water (90 mL) were mixed and stirred. Isoquinoline-5-carbonitrile (6 g, 38.62 mmol) obtained in Step (1) above and distilled water (90 mL) were mixed and stirred. The reaction solution was added with concentrated HCl solution (15 mL) and stirred for about 6 hours at 100C. The reaction mixture was cooled to room temperature and adjusted to have a pH value in a range of 5'6 by adding DIPEA (about 40 mL). The resulting solid mixture was stirred for about 3 hours at room temperature and filtered. The residue was dried in an oven at 50C to obtain the title compound (5.6 g, 84 %). MS (ESI+, m/z): 174 [M+H]+Isoquinoline-5-carbonitrile (6 g, 38.62 mmol) obtained in Step (1) above and distilled water (90 mL) were mixed and stirred. The reaction solution was added with concentrated HCl solution (15 mL) and stirred for about 6 hours at 100 C. The reaction mixture was cooled to room temperature and adjusted to have a pH value in a range of 5'6 by adding DIPEA (about 40 mL). The resulting solid mixture was stirred for about 3 hours at room temperature and filtered. The residue was dried in an oven at 50 C. to obtain the title compound (5.6 g, 84%). MS (ESI+, m/z): 174 [M+H]+This solid was redissolved in 300 mL of water, and the resultant solution was adjusted to pH 6 using a dilute ammonium hydroxide solution, resulting in the precipitation of a brown solid. This solid was isolated using filtration, azeotroped with benzene, and then dried at 130 C. under reduced pressure for approximately 3 hours to provide 5.7 g of a fine dark tan powder (m.p. 270-272 C.). Yield: 78%. 1 H NMR (DMSO): delta 13.4 (br.s, 1H), 8.69 (d, 1H, J=6.00 Hz), 8.58 (d, 1H, J=4.6 Hz), 8.40 (d, 1H, J=7.37 Hz), 8.36 (d, 1H, J=8.12 Hz), 7.74 (t, 1H, J=7.76); IR (KBr): 3460, 3014, 2930, 2851, 2777, 2405, 1912, 1711, 1622, 1574, 1493, 1427, 1375, 1264, 1211, 1152, 1044.General procedure: To a stirring solution of corresponding picolinic or nicotinic acids (1.0 eq.), EDCI (1.5 eq.) and HOBt (1.0 eq.)in CH2Cl2 at room temperature was added Et3N (2 eq.) dropwise, followed by the amine. The resultedmixture was stirred for 16 h and afterwards diluted by excess amount of CH2Cl2. The organic solution waswashed by water and dried over Na2SO4. A yellow residue was obtained after concentration and purified byflash column on silica gel to afford compound S2. To a solution of S2 (1.0 eq.) in THF at 78 was addedn-BuLi (1.1 eq.) or LDA (1.1 eq.) dropwise. The resulted mixture was stirred at this temperature for 15 min.A solution of corresponding acryloyl chloride (1.3 eq. while using n-BuLi and 2.5 eq. while using LDA) wasadded dropwise at 78. The reaction was warmed to room temperature gradually and stirred for another5 h . Afterwards, the reaction mixture was diluted with EtOAc and the organic solution was washed bywater and dried over Na2SO4. A brown residue was obtained after concentration and purified by flashcolumn on silica gel to afford the compound 4. Analytical data of 4q and 4r are consistent with the previousreportsA round bottom flask was charged with

Molecular Weight:173.17
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:173.047678466
Monoisotopic Mass:173.047678466
Topological Polar Surface Area:50.2
Heavy Atom Count:13
Complexity:205
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes