Structure of 13519-75-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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| CAS No. : | 13519-75-0 |
| Formula : | C8H10ClN |
| M.W : | 155.63 |
| SMILES Code : | CCNC1=CC=C(Cl)C=C1 |
| MDL No. : | MFCD00018594 |
| InChI Key : | KLWDPIXDUVYHMS-UHFFFAOYSA-N |
| Pubchem ID : | 587841 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302-H315-H319-H335 |
| Precautionary Statements: | P261-P305+P351+P338 |
* 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.

[ 13519-75-0 ]
[ 536-38-9 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 70% | With C20H25Cl2CoN3; sodium triethylborohydride; In 1,2-dimethoxyethane; at 100℃; for 6h;Inert atmosphere; | Under an inert atmosphere, the substrate 4-chloroacetanilide (170 mg, 1 mmol), polymethylhydrosiloxane (668 μL, 3 mmol), Co-2 catalyst (9.0 mg, 0.02 mmol), sodium triethylborohydride (40 μL, 0.04 mmol)were sequentially added to the reaction tube and ethylene glycol dimethyl ether (2 mL), and the resulting mixture was stirred well.The reaction was carried out in an oil bath at 100C for 6 hours. The reaction system was cooled to room temperature, diluted and quenched by adding ethyl acetate, and concentrated. The crude product was subjected to flash silica gel column chromatography to obtain 109 mg of light yellow oily liquid, yield: 70%. |
[ 104-15-4 ]
[ 13519-75-0 ]


[ 13519-75-0 ]

[ 13519-75-0 ]
[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In hexane; toluene; at 10 - 20℃; | To a solution of iV-ethyl-4-chloroaniline (650 mg, 4.18 mmol) in anhydrous toluene at 10 0C was slowly added a 2M solution of trimethylaluminium in hexanes (2.1 mL, 4.18 mmol). The reaction mixture was stirred at room temperature until gas evolution stopped. A second round bottom flask was charged with cw-2-methyl-l-(pyridine-4-carbonyl)-l,2,3,4-tetrahydro-quinoline-4- carboxylic acid methyl ester (370 mg, 1.19 mmol) and the preformed aluminum amide was added. The resulting reaction mixture was refluxed for 20 hours. The reaction was concentrated, quenched with IM aqueous hydrochloric acid at 0 0C (exothermic.), basified with IM aqueous sodium hydroxide, and extracted with ethyl acetate. The resulting organic layer was separated, washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford an orange oil which was purified via flash chromatography (1% methanol / methylene chloride) followed by HPLC to provide (+/-)-frøtts-2-methyl-l-(pyridine-4-carbony I)- 1,2,3, 4-tetrahydro-quinoline-4- EPO <DP n="96"/>carboxylic acid (4-chloro-phenyl)-ethyl-amide (11%). 1H-NMR (CDCl3) δ: 1.02 - 1.18 (m, 6H), 1.60- 1.70 (m, IH), 2.45 - 2.55 (m, IH), 3.60 - 3.70 (m, IH), 3.80 (q, 2H), 4.98 - 5.10 (m, IH), 6.40 (d,IH), 6.90 (m, 2H), 7.00 (t, IH), 7.30 (m, 2H), 7.50 (d, 2H), 7.60 (d, 2H), 8.55 (d, 2H). MS m/z:434/436 (M+l). |

[ 13519-75-0 ]

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 39% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 18 - 20h; | A round bottom flask with magnetic stirrer was charged with 2-methyl-l-(4- trifluoromethyl-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (886 mg, 2.44 mmol) in anhydrous pyridine (25.0 mL). To the reaction was added <strong>[13519-75-0]N-ethyl-p-chloroaniline</strong> (0.410 mL, 2.95 mmol), followed by EDCI (833 mg, 4.34 mmol). The reaction was stirred at room temperature under an argon atmosphere for 18-20 hours. The reaction was poured into a 1:1 mixture of water/brine (50 mL) and extracted with ethyl acetate (3 x 35 mL). The combined extractions were washed with brine (1 x 50 mL), dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford a brown residue. The residue was purified via silica gel chromatography (hexanes / ethyl acetate) to yield (+/-)-trans-2-methyl-l-(4-trifluoromethyl-benzoy I)- 1,2,3, 4-tetrahydro-quinoline-4- carboxylic acid (4-chloro-phenyl)-ethyl-amide (39%). 1H-NMR (CDCl3) δ: 1.02 (d, 3H), 1.12 (t, 3H), 1.64 - 1.74 (m, IH), 2.49 - 2.58 (m, IH), 3.59 - 3.72 (m, IH), 3.77 - 3.90 (m, 2H), 5.03 - 5.14 (m, IH), 6.35 - 6.41 (m, IH), 6.74 - 6.84 (m, 2H), 6.89 - 6.95 (m, IH), 7.17 - 7.25 (m, 2H), 7.44 - 7.52 (m, 2H), 7.63 - 7.69 (m, 2H). MS m/z: 501 (M+l). |

[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 14% | With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 20℃; for 18 - 20h; | A round bottom flask with magnetic stirrer was charged with l-(6-methoxy-pyridine-3- carbonyl)-2-methyl-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (190 mg, 0.58 mmol) in anhydrous pyridine (1.5 mL). To the reaction was added <strong>[13519-75-0]N-ethyl-p-chloroaniline</strong> (185 mg, 1.19 mmol), followed by EDCI (156 mg, 0.82 mmol). The reaction was stirred at room temperature under an argon atmosphere for 18 - 20 hours. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated in vacuo to afford a yellow oil (350 mg). The crude material was purified via silica gel EPO <DP n="85"/>chromatography (1 % methanol / methylene chloride) followed by HPLC to yield (+/-)-trans-l-(6- methoxy-pyridine-3-carbonyl)-2-methyl-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro- phenyl)-ethyl-amide (14%). 1H-NMR (CDCl3) δ: 1.05 (d, 3H), 1.13 (t, 3H), 1.65 - 1.75 (m, IH), 2.50 - 2.60 (m, IH), 3.60 - 3.70 (m, IH), 3.80 (q, 2H), 3.95 (s, 3H), 5.02 - 5.10 (m, IH), 6.50 (d, IH), 6.60 (d, IH), 6.75 (d, IH), 6.85 - 7.00 (m, 2H), 7.20 (m, 2H), 7.50 (d, 2H), 7.75 (d,lH), 8.40 (s, IH). MS m/z: 464/466 (M+l). |

[ 13519-75-0 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | l-(4-Methoxy-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (approx. 1.47 mmol) was suspended in methylene chloride (10 mL) to which one drop of dimethylformamide was added. Oxalyl chloride (375 mg, 275 uL, 2.95 mmol) was added. Vigorous bubbling ensued, followed by dissolution of the starting material. After stirring for 4 hours at room temperature, the yellow solution was concentrated and azeotroped with toluene to remove excess oxalyl chloride. The resulting acid chloride solution was dissolved in methylene chloride (10 mL). Diisopropylethylamine (569 mg, 768 uL, 4.41 mmol) was added, followed by <strong>[13519-75-0]4-chloro-N-ethylaniline</strong> (457 mg, 2.93 mmol). The mixture was stirred at room temperature overnight. The reaction was poured into ethyl acetate and washed with water and brine. The combined organics were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (ethyl acetate / hexanes gradient) to afford (+/-)-l-(4-methoxy-benzoyl)-l,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (193 mg) as a foam. 1H-NMR (CDCl3) δ: 1.17 (t, 3H), 2.06 - 2.26 (m, 2H), 3.57 - 3.70 (m, 2H), 3.73 - 3.87 (m, 5H), 4.02 (dd, IH), 6.52 (d, IH), 6.66 - 6.74 (m, 2H), 6.84 (ddd, IH), 6.93 - 7.06 (m, 2H), 7.17 - 7.24 (m, 2H), 7.37 - 7.43 (m, 2H). MS m/z: 449 (M+l). |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 72h; | Example 15 (4-Chloro-phenyl)-ethyl-((2S,4S)-4-fluoro-pyrrolidin-2-ylmethyl)-amine To a solution of N-ethyl-4-chloro-aniline (0.31 g, 2.0 mmol) in dichloromethane (8 ml) were added (2S,4S)-tert-butyloxycarbonyl-4-fluoro-pyrrolidine-2-carboxylic acid (0.47 g, 2.0 mmol), bis(2-oxo-3-oxazolidinyl)-phosphinic chloride (0.76 g, 3.0 mmol) and diisopropylethylamine (0.39 g, 3.0 mmol). The mixture was stirred for 3 days at room temperature. Aqueous sodium bicarbonate solution (20 ml) was added and the mixture was extracted with dichloromethane (3*20 ml). The combined organic layers were dried with magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (SiO2: heptane/ethyl acetate=2:1) to yield a light yellow oil (0.55 g), that was dissolved in tetrahydrofurane (15 ml). Borane-tetrahydrofurane-complex (7.4 ml, 1M, 7.4 mmol) was added and the mixture was heated at 60 C. overnight. After cooling 5 drops of aqueous hydrochloric acid (4N) were added and the solvent was evaporated. The white residue was dissolved in aqueous hydrochloric acid (4N, 10 ml) and heated at 60 C. for 1 hour. After cooling aqueous sodium hydroxide solution was added until basic pH and the mixture was extracted with dichloromethane (2*30 ml). The combined organic layers were dried with magnesium sulphate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (column: Isolute Flash-NH2 from Separtis; eluent: ethyl acetate/heptane 1:1) to yield a light yellow oil, (0.137 g, 27%); MS (ISP): 257.1 ((M+H)+.). |

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