3-isoquinolinecarboxaldehyde

Isoquinoline-3-carbaldehyde; A solution of methyl 3-isoquinolinecarboxylate (2. 0 g, 10.7 mmol) in toluene was cooled to-78°C. To the solution was added diisobutylaluminum hydride (1M in toluene, 21.4 mL, 21.4 mmol) slowly over 15 minutes via syringe. While still at-78°C, the reaction was quenched with a solution of ether (80 mL), acetic acid (20 mL) and water (8 mL) and then the mixture was allowed to slowly warm to room temperature overnight. The organics were decanted and the solvent was evaporated. Flash column chromatography (gradient 1: 4 ethyl acetate/hexanes to 1: 3 ethyl acetate/hexanes) provided 1.1 grams of the title compound (65percent yield).'H-NMR (CDC13, 300 MHz) 8 10.24 (s, 1H), 9.35 (s, 1H), 8.36 (s, 1H), 8.07-7. 98 (m, 2H), 7.82-7. 32 (m, 2H). Mass spec.: 158 (MH) +.To a cooled solution 0°C of isoquinoline-3-carboxylic acid methyl ester (l. Og, 5.34mmol) in anhydrous tetrahydrofuran (100ml), is added a solution of DIBAL-H (11. 8ml, 11. 8mmol). The reaction mixture is stirred at 0°C for 2 hours and then quenched with saturated aqueous sodium potassium tartrate and stirred for 2 hours. The layers are separated and the aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with 1N HCl, 2N NaOH, and dried over anhydrous Na2S04, filtered, and concentrated ira vacuo. The crude reaction mixture is purified on silica gel eluting with 20percent ethyl acetate/hexanes to give isoquinoline-3-carboxaldehyde (0.46g, 54percent).'H NMR (CDC13) : 8 = 10.24 (1H, brs), 9.32 (1H, brs), 8.35 (1H, brs), 8. 02 (2H, brd), 7.77 (2H, brs).Example 11;: 3-Amino-6- [4- (2-hydroxy-2-isoquinolin-3-yl-ethylamino)-piperidin-1-yl]- 4-propyl-thieno [2, 3-b] pyridine-2-carboxylic acid amide Methyl 3-isoquinoline carboxylate (1.50 g, 8.01 mmol) was placed in 60 mL anhydrous toluene and cooled to 0 °C. The solution was treated dropwise with 1M DIBAL solution in toluene (8.2 mL, 8.2 mmol). The solution gradually changed from colorless to yellow and then orange during addition. After 2 h another 2 mL 1M DIBAL solution in toluene was added and the mixture was left stirring another 1 h at 0-10 °C. The mixture was then quenched with aqueous Na K tartrate solution, stirred 15 min then diluted with brine and EtOAc. The layers were separated and the aqueous was extracted twice with EtOAc. The combined organics were washed with brine repeatedly (emulsion), dried (MgS04), filtered and the solvent was removed in vacuo. An orange oil was thus obtained, which was purified by flash column chromatography on Si02 using CH2Cl2/MeOH eluent mixtures. The desired isoquinoline carboxaldehyde was isolated as a yellow solid, 420 mg (33percent of theory).

Molecular Weight:157.17
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:157.052763847
Monoisotopic Mass:157.052763847
Topological Polar Surface Area:30
Heavy Atom Count:12
Complexity:169
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes