(2E)-3-[2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-2-propenal

The same operation as in was performed except that ethylidenecyclohexylamine (1.7 g, 13.8 mmol) was used instead of ethylidene tert-butylamine (1.4 g, 14.1 mmol). A part of the obtained reaction mixture was poured into the 10 mass percent aqueous acetic acid solution, and an analysis by internal standard methods was performed using high performance liquid chromatography. As a result, (E) -3- (4'-(4-fluorophenyl)-2'-cyclopropylquinolin-3'-yl)propenaldehyde (1.7 g, 5.4 mmol, yield 78.3percent) was found to have been produced. 4-(4'-Fluorophenyl)-2-cyclopropylquinoline-3-carbaldehyde (2.0 g, 6.9mmol), ethylidene tert-butylamine (1.4 g, 14.1 mmol) and tetrahydrofuran (10 ml) were charged in a 50 ml three-neck flask equipped with a thermometer, a magnetic stirrer and a nitrogen balloon and the mixture was heated to 63°C. Sodium hydride (60 mass percent, 0.44 g, 11.0 mmol) was added over 3 hrs. After completion of the addition, the mixture was further stirred for 8 hrs. A part of the obtained reaction mixture was poured into the 10 mass percent aqueous acetic acid solution, and an analysis by internal standard methods was performed using high performance liquid chromatography. As a result, (E)-3-(4'-(4-fluorophenyl)-2'-cyclopropylquinolin-3'-yl)propenaldehyde (1.5 g, 4.7 mmol, yield 68.0percent) was found to have been produced. melting point: 124-132°C The same operation as in was performed except that ethylidene n-butylamine (1.4 g, 14.1 mmol) was used instead of ethylidene tert-butylamine (1.4 g, 14.1 mmol). A part of the obtained reaction mixture was poured into the 10 mass percent aqueous acetic acid solution, and an analysis by internal standard methods was performed using high performance liquid chromatography. As a result, (E)-3-(4'-(4-fluorophenyl)-2'-cyclopropylquinolin-3'-yl)propenaldehyde (1.3 g, 4.2 mmol, yield 60.3percent) was found to have been produced.60% NaH 80·35 g (2.01 mol, 2.55 eq) and 2.5L anhydrous THF (Tetrahydrofuran) was added to in a 10 L three-necked flask, and the mixture was stirred under a nitrogen atmosphere at a temperature of -25 C, and 174.28 g of the compound II (1.34 mil, 1.7 eq), was added dropwise and stirred under nitrogen for 2 h, A 2.5 M solution of n-butyllithium in n-hexane was added dropwise 662 mL (1.65 mol, 2 leq), stirred for 2 h, Finally, the compound I 250g (787.75 mmol, leq) was added dropwise 2.5 L of anhydrous THF solution, stirred for 3 h, TLC detection of the basic reaction is complete. The reaction was quenched by the addition of 2 L of saturated aqueous ammonium chloride solution, Ether extraction 1L X 3 times, combined with organic phase, Purified washed 1L X 2 times, Na2SO4 dry, filtered, In 30 C ~ 40 C water bath rotation concentrated to dry, The crude product of compound m was 325 g. Yield 92.2%, determination of Chemical Purity by 87.2%.60% NaH 80·35 g (2.01 mol, 2.55 eq) and 2.5L anhydrous THF (Tetrahydrofuran) was added to in a 10 L three-necked flask, and the mixture was stirred under a nitrogen atmosphere at a temperature of -25 C, and 283.96 g of the compound II (1.97 mol, 2.5 eq), was added dropwise and stirred under nitrogen for 2 h, A 2.5 M solution of n-butyllithium in n-hexane was added dropwise 662 mL (1.65 mol, 2.1 eq), stirred for 2 h, Finally, the compound I 250g (787.75 mmol, 1 eq) was added dropwise 2.5 L of anhydrous THF solution, stirred for 3 h, TLC detection of the basic reaction is complete. The reaction was quenched by the addition of 2 L of saturated aqueous ammonium chloride solution, Ether extraction 700 ml X 3 times, combined with organic phase, Purified washed 1L X 2 times, Na2SO4 dry, filtered, for 30 C ~ 40 C water bath rotation concentrated to dry, The crude product of compound m was 338.12 g. Yield 93 %, determination of Chemical Purity by 86%.60% NaH 80·35 g (2.01 mol, 2.55 eq) and 2.5L anhydrous THF (Tetrahydrofuran) was added to in a 10 L three-necked flask, and the mixture was stirred under a nitrogen atmosphere at a temperature of -25 C, and 137.05 g of the compound II (1.18 mol, 1.5 eq), was added dropwise and stirred under nitrogen for 2 h, A 2.5 M solution of n-butyllithium in n-hexane was added dropwise 662 mL (1.65 mol, 2.1 eq), stirred for 2 h, Finally, the compound I 250g (787.75 mmol, 1 eq) was added dropwise 2.5 L of anhydrous THF solution, stirred for 3 h, TLC detection of the basic reaction is complete. The reaction was quenched by the addition of 2 L of saturated aqueous ammonium chloride solution, Ether extraction 1L X 3 times, combined with organic phase, Purified washed 1L X 2 times, Na2SO4 dry, filtered, for 30 C ~ 40 C water bath rotation concentrated to dry, The crude product of compound m was 309.37g. Yield 90.6%, determination of Chemical Purity by 89%.

Molecular Weight:317.4
XLogP3:4.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:317.121592296
Monoisotopic Mass:317.121592296
Topological Polar Surface Area:30
Heavy Atom Count:24
Complexity:467
Defined Bond Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes