METHYL6-QUINOLINEACETATE

Preparation of 6-((5)-l-(6-(l-methyl-lH-pyrazol-4-yl)-[l, 2, 4]triazolo[3, 4- δ][l, 3, 4]thiadiazol-3-yl)ethyl)quinoline (compound 1); [0064] As shown in step i of Scheme 1, concentrated sulfuric acid (206 mL, 3.868 mol) was added dropwise to a solution of 2-(quinolin-6-yl)acetic acid (compound 1001, 658.2 g, 3.516 mol, Okeanos Tech Co., Cat. No. OK-J-05024) in 6.5 liters of methanol. During the addition, a slight exotherm was observed. After the addition was complete, the reaction was stirred at reflux for 4 hours. After cooling, the volatiles were removed under reduced pressure, the resulting residue was diluted with 4 liters of ethyl acetate, cooled in an ice bath, treated with 2N NaOH (2.1 liters, 1.2 equiv.) until a pH of 4 was achieved, and then treated with saturated sodium bicarbonate until a pH of 8 was achieved. The layers were separated and the aqueous layer extracted twice with ethyl acetate. The combined organics were washed with saturated sodium bicarbonate, washed with water, washed with brine, dried over anhydrous MgSOTo a solution of 2-(quinolin-6-yl)acetic acid (2.0 g, 11 mmol) in methanol (40 mL) wasadded concentrated sulphuric acid (0.2 mL). The mixture was stirred at roomtemperature for 6 hours. The reaction mass was poured into water and the resulting solution was neutralised with saturated NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2504 and evaporated in vacuo to give methyl 2-(quinolin-6-yl)acetate (1.8 g, 85percent). LCMS: m/z202.25 [M+H].2-(quinolin-6-yl)acetic acid (12.0 g, 0.064 mol) was dissolved in dry MeOH (120 mL) and cooled to 0 °C. SOClTo a stirred solution of quinolin-6-yl-acetic acid (10 g, 53.0 mmol) in 100 ml of methanol was added 2.5 ml of concentrated HTo a suspension of compound 2 (60 g, 0.32 mol) in MeOH (600 mL) cooled to 0~5°C, SOCIExample 1. Preparation of 6-((5)-l-(6-(l-methyl-lH-pyrazol-4-yl)-[l, 2, 4]triazolo[3, 4- δ][l, 3, 4]thiadiazol-3-yl)ethyl)quinoline (compound 1); [0064] As shown in step i of Scheme 1, concentrated sulfuric acid (206 mL, 3.868 mol) was added dropwise to a solution of 2-(quinolin-6-yl)acetic acid (compound 1001, 658.2 g, 3.516 mol, Okeanos Tech Co., Cat. No. OK-J-05024) in 6.5 liters of methanol. During the addition, a slight exotherm was observed. After the addition was complete, the reaction was stirred at reflux for 4 hours. After cooling, the volatiles were removed under reduced pressure, the resulting residue was diluted with 4 liters of ethyl acetate, cooled in an ice bath, treated with 2N NaOH (2.1 liters, 1.2 equiv.) until a pH of 4 was achieved, and then treated with saturated sodium bicarbonate until a pH of 8 was achieved. The layers were separated and the aqueous layer extracted twice with ethyl acetate. The combined organics were washed with saturated sodium bicarbonate, washed with water, washed with brine, dried over anhydrous MgSOTo a solution of 2-(quinolin-6-yl)acetic acid (2.0 g, 11 mmol) in methanol (40 mL) wasadded concentrated sulphuric acid (0.2 mL). The mixture was stirred at roomtemperature for 6 hours. The reaction mass was poured into water and the resulting solution was neutralised with saturated NaHCO3 solution and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2504 and evaporated in vacuo to give methyl 2-(quinolin-6-yl)acetate (1.8 g, 85percent). LCMS: m/z202.25 [M+H].2-(quinolin-6-yl)acetic acid (12.0 g, 0.064 mol) was dissolved in dry MeOH (120 mL) and cooled to 0 °C. SOClTo a stirred solution of quinolin-6-yl-acetic acid (10 g, 53.0 mmol) in 100 ml of methanol was added 2.5 ml of concentrated HTo a suspension of compound 2 (60 g, 0.32 mol) in MeOH (600 mL) cooled to 0~5°C, SOCITo a 2-L round bottom flask was added

Molecular Weight:201.22
XLogP3:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:201.078978594
Monoisotopic Mass:201.078978594
Topological Polar Surface Area:39.2
Heavy Atom Count:15
Complexity:230
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes