Isoquinoline-4-carboxylicacid

To a stirred solution of isoquinolin-4-carbonitrile (Intermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with Etlntermediate-14: lsoquinolin-4-carboxylic acid: To a stirred solution of isoquinolin-4-carbonitrile (lntermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with EtTo a stirred solution of isoquinolin-4-carbonitrile (Intermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with Etlntermediate-14: lsoquinolin-4-carboxylic acid: To a stirred solution of isoquinolin-4-carbonitrile (lntermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with EtTo a stirred solution of isoquinolin-4-carbonitrile (Intermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with Et2O and neutralized using 1N HCl. It was extracted with EtOAc and the organic layer was dried over Na2SO4, filtered, and concentrated to give the title compound (2 g, 59.3percent) as an off white solid.lntermediate-14: lsoquinolin-4-carboxylic acid: To a stirred solution of isoquinolin-4-carbonitrile (lntermediate-13) (3.0 g, 19.45 mmol) in EtOH (30 mL) was added KOH (20 g in 20 mL water) and the mixture was refluxed overnight. It was then cooled to RT and concentrated under reduced pressure. The aqueous layer was washed with Et20 and neutralized using 1 N HCI. It was extracted with EtOAc and the organic layer was dried over Na2S04, filtered, and concentrated to give the title compound (2 g, 59.3percent) as an off white solid.General procedure: To a suspension of the acid(0.25 mmol, 1.00 equiv) and N, N, N0 , N0-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (0.25 mmol, 1.00 equiv) in CH2Cl2 (2.5 mL), under an air atmosphere, at ambienttemperature, was added diisopropylethylamine (0.1 mL, 0.58 mmol, 2.34 equiv) and the mixture was stirred for 25 min.2-((5-(Trifluoromethyl)pyridin-2-yl)sulfonyl)ethan-1-aminiumchloride(14) (0.26 mmol, 1.05 equiv) and CH2Cl2 (5 mL) were thenadded and the mixture was stirred for 48 h. The reaction wasquenched with aqueous HCl (1 M, 2 mL), followed by H2O(10 mL) and EtOAc (20 mL). The mixture was transferred to a separatoryfunnel and the flask rinsed with EtOAc (10 mL). The organicphase was separated, washed with saturated aqueous NaHCO3(15 mL) and dried over anhydrous Na2SO4. The solvent was thenremoved under reduced pressure, at or below 40 C, to afford thecrude product. Purification was performed as indicated for eachcompound below 5.3.6.16 N-(2-((5-(Trifluoromethyl)pyridin-2-yl)sulfonyl)ethyl)isoquinoline-4-carboxamide (46) The title compound was prepared from

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