Structure of 214476-78-5
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CAS No. : | 214476-78-5 |
Formula : | C11H7ClN2O |
M.W : | 218.64 |
SMILES Code : | N#CC1=C(Cl)C2=CC=CC(OC)=C2N=C1 |
MDL No. : | MFCD09261369 |
InChI Key : | JSPIITUWOZXTTO-UHFFFAOYSA-N |
Pubchem ID : | 22466699 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P280 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With trichlorophosphate;N,N-dimethyl-formamide; for 0.5h;Heating / reflux; | A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy-3-quinolinecarbonitrile as an off white solid in 91 % yield, mass spectrum (electrospray, m/e): M+H 219.1. |
With trichlorophosphate;N,N-dimethyl-formamide; for 0.5h;Heating / reflux; | A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-quinoline-3-carbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy -quinoline-3-carbonitrile as an off white solid in 91 % yield, mass spectrum (electrospray, m/e): M+H 219.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.6% | With pyridine hydrochloride; In 2-ethoxy-ethanol; for 0.5h;Heating / reflux; | A solution of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 309.7 mg (1.8 mmol) of 3-bromoaniline and 173.3 mg (1.5 mmol) of pyridine hydrochloride in 15 ml of 2-ethoxyethanol was refluxed under nitrogen for 0.5 hours. The solvent was removed and the residue was diluted with water followed by neutralization to pH 7-8 with diluted sodium carbonate solution . The precipitate was collected and washed with ether and dried in vacuo to give 476.1 mg (89.6%) of the product as a yellow solid, m.p. 210-212 C; mass spectrum (electrospray, m/e): M+H 353.8, 355.8. |
476.1 mg (89.6%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 274 4-[(3-Bromophenyl)amino]-8-methoxy-3-quinolinecarbonitrile A solution of 328.0 mg (1.5 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 309.7 mg (1.8 mmol) of 3-bromoaniline and 173.3 mg (1.5 mmol) of pyridine hydrochloride in 15 ml of 2-ethoxyethanol was refluxed under nitrogen for 0.5 hours. The solvent was removed and the residue was diluted with water followed by neutralization to pH 7-8 with diluted sodium carbonate solution. The precipitate was collected and washed with ether and dried in vacuo to give 476.1 mg (89.6%) of the product as a yellow solid, m.p. 210-212 C.; mass spectrum (electrospray, m/e): M+H 353.8, 355.8. |
476.1 mg (89.6%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 274 4-[(3-Bromophenyl)amino]-8-methoxy -3-quinolinecarbonitrile A solution of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 309.7 mg (1.8 mmol) of 3-bromoaniline and 173.3 mg (1.5 mmol) of pyridine hydrochloride in 15 ml of 2-ethoxyethanol was refluxed under nitrogen for 0.5 hours. The solvent was removed and the residue was diluted with water followed by neutralization to pH 7-8 with diluted sodium carbonate solution. The precipitate was collected and washed with ether and dried in vacuo to give 476.1 mg (89.6%) of the product as a yellow solid, m.p. 210-212 C.; mass spectrum (electrospray, m/e): M+H 353.8, 355.8. |
476.1 mg (89.6%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 274 4-[(3-Bromophenyl)amino]-8-methoxy-3-quinolinecarbonitrile A solution of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 309.7 mg (1.8 mmol) of 3-bromoaniline and 173.3 mg (1.5 mmol) of pyridine hydrochloride in 15 ml of 2-ethoxyethanol was refluxed under nitrogen for 0.5 hours. The solvent was removed and the residue was diluted with water followed by neutralization to pH 7-8 with diluted sodium carbonate solution. The precipitate was collected and washed with ether and dried in vacuo to give 476.1 mg (89.6%) of the product as a yellow solid, m.p. 210-212 C; mass spectrum (electrospray, m/e): M+H 353.8, 355.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
261.6 mg (89.0%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 279 4-(3-Hydroxy-4-methoxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 200.0 mg (0.92 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 105.7 mg (0.92 mmol) of pyridine hydrochloride and 140.6 mg (1.0 mmol) of 5-amino-2-methoxy-phenol in 10 mL of 2-ethoxyethanol was heated at 100 C. for 2 hr. The work up gave 261.6 mg (89.0%) of the product as a deep yellow solid, m.p. 138-140 C. (dec.), mass spectrum (electrospray, m/e): M+H 321.9. |
261.6 mg (89.0%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 279 4-(3-Hydroxy-4-methoxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 200.0 mg (0.92 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 105.7 mg (0.92 mmol) of pyridine hydrochloride and 140.6 mg (1.0 mmol) of 5-amino-2-methoxyphenol in 10 mL of 2-ethoxyethanol was heated at 100 C. for 2 hr. The work up gave 261.6 mg (89.0%) of the product as a deep yellow solid, m.p. 138-140 C. (dec.), mass spectrum (electrospray, m/e): M+H 321.9. |
261.6 mg (89.0%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 279 4-(3-Hydroxy-4-methoxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 200.0 mg (0.92 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 105.7 mg (0.92 mmol) of pyridine hydrochloride and 140.6 mg (1.0 mmol) of 5-amino-2-methoxy--phenol in 10 mL of 2-ethoxyethanol was heated at 100 C for 2 hr. The work up gave 261.6 mg (89.0 %) of the product as a deep yellow solid, m.p. 138-140C (dec.), mass spectrum (electrospray, m/e): M+H 321.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 275 4-(4-Chloro-2-fluoro-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 240.0 mg (1.7 mmol) of 2-fluoro-4-chloro-aniline in 15 mL of 2-ethoxyethanol was heated at 100 C. for 2 hr. After the work up, 431.3 mg (87.9%) of the product was obtained as an off white solid, m.p. 127 C. (dec.), mass spectrum (electrospray, m/e): M+H 327.8, 329.9. | |
With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 275 4-(4-Chloro-2-fluoro-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 240.0 mg (1.7 mmol) of 2-fluoro-4-chloroaniline in 15 mL of 2-ethoxyethanol was heated at 100 C. for 2 hr. After the work up, 431.3 mg (87.9%) of the product was obtained as an off white solid, m.p. 127 C. (dec.), mass spectrum (electrospray, m/e): M+H 327.8, 329.9. | |
With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 275 4-(4-Chloro-2-fluoro-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 240.0 mg (1.7 mmol) of 2-fluoro-4-chloro-aniline in 15 mL of 2-ethoxyethanol was heated at 100 C for 2 hr. After the work up, 431.3 mg (87.9%) of the product was obtained as an off white solid, m.p. 127 C (dec.), mass spectrum (electrospray, m/e): M+H 327.8, 329.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
294.8 mg (73.4%) | With pyridine; In 2-ethoxy-ethanol; | EXAMPLE 277 4-(3-Dimethylamino-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 250.0 mg (1.1 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 273.3 mg (3.0 mmol) of pyridine and 261.4 mg (1.25 mmol) of 3-dimethylaminoaniline hydrochloride in 10 mL of 2-ethoxyethanol was heated at 100 C. for 1.5 hr. The work up gave 294.8 mg (73.4%) of the product as a deep greenish yellow solid, m.p. 222-225 C., mass spectrum (electrospray, m/e): M+H 319.0. |
294.8 mg (73.4%) | With pyridine; In 2-ethoxy-ethanol; | EXAMPLE 277 4(3-Dimethylamino-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 250.0 mg (1.1 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 273.3 mg (3.0 mmol) of pyridine and 261.4 mg (1.25 mmol) of 3-dimethylaminoaniline hydrochloride in 10 mL of 2-ethoxyethanol was heated at 100 C. for 1.5 hr. The work up gave 294.8 mg (73.4%) of the product as a deep greenish yellow solid, m.p. 222-225 C., mass spectrum (electrospray, m/e): M+H 319.0. |
294.8 mg (73.4%) | With pyridine; In 2-ethoxy-ethanol; | Example 277 4-(3-Dimethylamino-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 250.0 mg (1.1 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 273.3 mg (3.0 mmol) of pyridine and 261.4 mg (1.25 mmol) of 3-dimethylaminoaniline hydrochloride in 10 mL of 2-ethoxyethanol was heated at 100C for 1.5 hr. The work up gave 294.8 mg (73.4%) of the product as a deep greenish yellow solid, m.p. 222-225 C, mass spectrum (electrospray, m/e): M+H 319.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With sodium carbonate; In N,N-dimethyl-formamide; | EXAMPLE 273 4-Chloro-8-methoxy -3-quinolinecarbonitrile A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy -3-quinolinecarbonitrile as an off white solid in 91% yield, mass spectrum (electrospray, m/e): M+H 219.1. |
91% | With sodium carbonate; In N,N-dimethyl-formamide; | EXAMPLE 273 4-Chloro-8-methoxy-3-quinolinecarbonitrile A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy-3-quinolinecarbonitrile as an off white solid in 91% yield, mass spectrum (electrospray, m/e): M+H 219.1. |
91% | With sodium carbonate; In N,N-dimethyl-formamide; | EXAMPLE 92 4-Chloro-8-methoxy-quinoline-3-carbonitrile A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-quinoline-3-carbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy-quinoline-3-carbonitrile as an off white solid in 91% yield, mass spectrum (electrospray, m/e): M+H 219.1. |
91% | With sodium carbonate; In N,N-dimethyl-formamide; | Example 273 4-Chloro-8-methoxy-3-quinolinecarbonitrile A mixture of 3.8 g (19 mmol) of 1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarbonitrile and 40 mL of phosphorous oxochloride and 5 drops of DMF was refluxed for 0.5 hours. The mixture was evaporated to dryness and diluted with hexanes. The solid was collected and mixed with cold dilute sodium carbonate solution and extracted several times with ethyl acetate. The organic layer was dried over sodium sulfate and filtered through a pad of silica gel. Removal of the solvent gave 3.8 g of 4-chloro-8-methoxy-3-quinolinecarbonitrile as an off white solid in 91 % yield, mass spectrum (electrospray, m/e): M+H 219.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
374.1 mg (88.6%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 278 4-(4-Bromo-3-hydroxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 250.0 mg (1.1 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 131.7 mg (1.1 mmol) of pyridine hydrochloride and 286.7 mg (1.3 mmol) of 4-bromo-3-hydroxy-aniline in 10 mL of 2-ethoxyethanol was heated at 100 C. for 1.5 hr. The work up gave 374.1 mg (88.6%) of the product as a pink solid, m.p. 146 C. (dec.), mass spectrum (electrospray, m/e): M+H 369.9. |
374.1 mg (88.6%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 278 4-(4-Bromo-3-hydroxy-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 250.0 mg (1.1 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 131.7 mg (1.1 mmol) of pyridine hydrochloride and 286.7 mg (1.3 mmol) of 4-bromo-3-hydroxyaniline in 10 mL of 2-ethoxyethanol was heated at 100 C for 1.5 hr. The work up gave 374.1 mg (88.6 %) of the product as a pink solid, m.p. 146 C (dec.), mass spectrum (electrospray, m/e): M+H 369.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 276 4-(3-Hydroxy-4-methyl-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 203.2 mg (1.7 mmol) of 3-hydroxy-4-methyl-aniline in 15 mL of 2-ethoxyethanol was heated at 100 C. for 1.5 hr. After the work up, 407.7 mg (89.4%) of the product was obtained as a yellow solid, m.p. 148-150 C., mass spectrum (electrospray, m/e): M+H 306.9. | |
With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 276 4-(3-Hydroxy-4-methyl-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 203.2 mg (1.7 mmol) of 3-hydroxy-4-methylaniline in 15 mL of 2-ethoxyethanol was heated at 100 C. for 1.5 hr. After the work up, 407.7 mg (89.4%) of the product was obtained as a yellow solid, m.p. 148-150 C., mass spectrum (electrospray, m/e): M+H 306.9. | |
With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 276 4-(3-Hydroxy-4-methyl-phenylamino)-8-methoxy-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 328.0 mg (1.5 mmol) of 4-chloro-8-methoxy -3-quinolinecarbonitrile, 173.3 mg (1.5 mmol) of pyridine hydrochloride and 203.2 mg (1.7 mmol) of 3-hydroxy-4-methylaniline in 15 mL of 2-ethoxyethanol was heated at 100 C for 1.5 hr. After the work up, 407.7 mg (89.4%) of the product was obtained as a yellow solid, m.p. 148-150C, mass spectrum (electrospray, m/e): M+H 306.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
112.6 mg (37.4%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | EXAMPLE 280 8-Methoxy-4-(2,4,6-trifluoro-phenylamino)-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 200.0 mg (0.92 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 105.7 mg (0.92 mmol) of pyridine hydrochloride and 148.6 mg (1.0 mmol) of 2,4,6-trifluoro-aniline in 10 mL of 2-ethoxyethanol was heated at 100 C. for 2 hr. The work up gave 112.6 mg (37.4%) of the product as a yellow solid, m.p. 297 C. (dec.), mass spectrum (electrospray, m/e): M+H 330.0. |
112.6 mg (37.4%) | With pyridine hydrochloride; In 2-ethoxy-ethanol; | Example 280 8-Methoxy-4-(2,4,6-trifluoro-phenylamino)-quinoline-3-carbonitrile Using an analogous procedure to that described in Example 274. A reaction mixture of 200.0 mg (0.92 mmol) of <strong>[214476-78-5]4-chloro-8-methoxy-3-quinolinecarbonitrile</strong>, 105.7 mg (0.92 mmol) of pyridine hydrochloride and 148.6 mg (1.0 mmol) of 2,4,6-trifluoro-aniline in 10 mL of 2-ethoxyethanol was heated at 100 C for 2 hr. The work up gave 112.6 mg (37.4 %) of the product as a yellow solid, m.p. 297 C (dec.), mass spectrum (electrospray, m/e): M+H 330.0. |
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