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Structure of 20260-53-1
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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. : | 20260-53-1 |
Formula : | C6H5Cl2NO |
M.W : | 178.02 |
SMILES Code : | O=C(Cl)C1=CN=CC=C1.[H]Cl |
MDL No. : | MFCD00012820 |
InChI Key : | MSYBLBLAMDYKKZ-UHFFFAOYSA-N |
Pubchem ID : | 88438 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
65% | With triethylamine; In dichloromethane; at 0 - 20℃; for 3h; | General procedure: A 25 mL round bottom flask initiallyplaced in an ice bath was charged with 0.629 g (3.389 mmol) ofisonicotinoyl chloride hydrochloride, 0.800 mL of triethylamine,8.00 mL of dichoromethane and 0.400 (1.64 mmol) of 2-(piperidin-1-yl)-5-(trifluoromethyl) aniline (8). The ice-bathwas removed andthe mixture was magnetically stirred at room temperature for 3 h.Then, 10.0 mL of distilled water was added, and the mixture wastransferred to a separatory funnel. The aqueous layer was extractedwith ethyl acetate (4 x 30.0 mL). The organic extracts were combinedand the resulting organic layer was washed with brine, driedover sodium sulphate, filtered, and concentrated under reducedpressure. The residue was purified by silica gel column chromatographyeluted with hexane-ethyl acetate (3:1 v/v). The solid wasfurther recrystallized with acetone. The compound SRPIN340 wasobtained as a white solid in 75% yield (430 mg, 1.23 mmol). |
45.3% | With triethylamine; In dichloromethane; at 0 - 20℃; for 16.5h; | Nicotinoyl chloride hydrochloride (122 mg, 0.685 mmol, commercially available product) and triethylamine (250 mul, 1.79 mmol) were sequentially added at 0C to a dichloromethane (5 ml) solution of <strong>[1496-40-8]2-(1-piperidinyl)-5-(trifluoromethyl)aniline</strong> (152 mg, 0.622 mmol), obtained as described in Referential Example 1-2. The resulting mixture was warmed to room temperature and stirred for 16.5 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (15 g, hexane/ethyl acetate = 1.5/1-1/1). Thus, N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]nicotinamide (GIF-0343) (98.4 mg, 45.3%) was yielded as a colorless solid. The melting point, and results of TLC and 1H NMR (CDCl3, 400 MHz), are as follows: m.p. 145-146C; TLC Rf 0.40 (hexane/ethyl acetate = 1/1); 1H NMR (CDCl3, 400 MHz) delta 1.62-1.69 (m, 2H, CH2), 1.79 (tt, 4H, J = 5.8, 5.8 Hz, 2CH2), 2.88 (t, 4H, J = 5.8 Hz, 2CH2), 7.29 (d, 1H, J = 8.4 Hz, aromatic), 7.39 (dd, 1H, J = 2.0, 8.4 Hz, aromatic), 7.51 (dd, 1H, J = 4.8, 8.0 Hz, aromatic), 8.30 (ddd, 1H, J = 1.6, 2.4, 8.0 Hz, aromatic), 8.82 (dd, 1H, J = 1.6, 4.8 Hz, aromatic), 8.87 (d, 1 H, J = 2.0 Hz, aromatic), 9.16 (d, 1 H, J = 2.4 Hz, aromatic), 9.53 (s, 1 H, NH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.7% | An acetonitrile (15 ml) solution containing potassium thiocyanate (119 mg, 1.22 mmol, commercially available product) and nicotinoyl chloride hydrochloride (352 mg, 1.97 mmol, commercially available product) was stirred at 70C for 40 minutes. The mixture was cooled to room temperature, and then an acetonitrile (5 ml) solution of <strong>[1496-40-8]2-(1-piperidinyl)-5-(trifluoromethyl)aniline</strong> (244 mg, 1.00 mmol), obtained as described in Referential Example 1-2, and triethylamine (278 mul, 2.00 mmol) were sequentially added thereto. The resulting mixture was stirred at 50C for one hour. Water was added to the mixture, and the resulting mixture was extracted three times with dichloromethane. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (25 g, hexane/ethyl acetate = 4/1-1/1). Thus, 1-nicotinoyl-3-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]thiourea (GIF-0624) (383 mg, 93.7%) was yielded as a pale yellow solid. The melting point, and results of TLC and 1H NMR (CD3OD, 400 MHz), are as follows: m.p. 142-144C; TLC Rf 0.26 (hexane/ethyl acetate = 1/1); 1H NMR (CDCl3, 400 MHz) delta 1.58-1.67 (m, 2H, CH2), 1.75-1.85 (m, 4H, 2CH2), 2.89-2.95 (m, 4H, 2CH2), 7.33-7.40 (m, 1H, aromatic), 7.44-7.48 (m, 1H, aromatic), 7.60-7.65 (m, 1H, aromatic), 8.76-8.78 (m, 1H, aromatic), 9.05 (s, 0.6H, aromatic), 9.09-9.14 (m, 1H, aromatic), 8.37-8.39 (m, 1H, aromatic), 8.49 (s, 0.4H, aromatic). | |
With triethylamine; In acetonitrile; | [Reference example 3] Synthesis of Compound 3 An acetonitrile (15 mL) solution of potassium thiocyanate (commercial product) (198 mg, 2.04 mmol) and nicotinoyl chloride hydrochloride (272 mg, 1.53 mmol; commercial product) was stirred at 80C for 1 hour. The mixture was left to room temperature. 2-(1-Piperidinyl)-5-(trifluoromethyl)aniline (250 mg, 1.02 mmol) obtained in Reference example 1-2 and triethylamine (285 muL, 2.04 mmol) were added sequentially to the mixture. The mixture was stirred at 50C for 1 hour. The mixture was poured into an aqueous saturated sodium bicarbonate solution and then the mixture was subjected to extraction with dichloromethane (x3). The thus obtained organic layer was washed with water, dried using anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate/dichloromethane = 6/3/4), so that 1-nicotinoyl-3-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]thiourea (Compound 3) (70.7 mg, 30.1%) was obtained as light yellow solid. The results of the melting point, TLC, 1H NMR (CD3OD, 400 MHz), and IR are as follows. Melting point 155-156C; TLC Rf 0.21 (hexane/ethyl acetate /dichloromethane =4/3/3); 1H NMR (CDCl3, 300 MHz) delta1.61 (m, 2H, J = 5.3 Hz, CH2), 1.81 (m, 4H, J = 5.3 Hz, 2CH2), 2.89 (t, 4H, J = 5.3 Hz, 2CH2), 7.24 (d, 1H, J = 8.4 Hz, aromatic), 7.47 (dd, 1H, J = 2.4, 8.4 Hz, aromatic), 7.52 (dd, 1H, J = 4.8, 8.0 Hz, aromatic), 8.23 (ddd, 1H, J = 1.7, 1.7, 8.0 Hz, aromatic), 8.89 (dd, 1H, J = 1.7, 4.8 Hz, aromatic), 9.09 (br s, 2H, aromatic, NH), 9.18 (d, 1H, J = 2.4 Hz, aromatic), 12.9 (br s, 1H, NH); IR (KBr, cm-1) 644, 704, 731, 804, 826, 883, 908, 1026, 1078, 1123, 1165, 1204, 1221, 1271, 1298,1335,1439,1479,1531,1587,1614,1678,2814,2855,2940. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In acetonitrile; at 0 - 20℃; for 16h; | At 0° C., a suspension of pyridine-3-carbonyl chloride hydrochloride (16.4 g, 92.0 mmol) in acetonitrile (300 ml) was added to a solution of <strong>[7321-93-9]4,6-dichloropyridine-3-amine</strong> (5.00 g, 30.7 mmol) inacetonitrile (120 ml) and pyridine (20 ml). The reaction mixture was stirred for 16 h at room temperature. Subsequently, water was added and the mixture was made alkaline with aqueous sodium hydroxide solution (1 M) and extracted with ethyl acetate. The combined organic phases were filtered and a precipitate was obtained. This precipitate was dried, thus isolating 2.86 g (100percent pure, 35percent yield) of N-(4,6-dichloro-3-pyridyl)pyridine-3-carbox- amide. The filtrate was dried with Na2504 and the solvent was removed under reduced pressure. This gave a further 5.44 g (92percent pure, 61percent yield) of N-(4,6-dichloro-3-pyridyl) pyridine-3-carboxamide. ?H-NMR (400.0 MHz, d5-DMSO): oe=9.165 (6.91);9.159 (7.23); 8.789 (4.49); 8.785 (4.83); 8.777 (4.84); 8.773(4.80); 8.659 (16.00); 8.354 (2.63); 8.349 (4.29); 8.344(2.75); 8.334 (2.88); 8.329 (4.55); 8.325 (2.84); 7.924 (15.29); 7.873 (1.12); 7.599 (3.76); 7.587 (3.77); 7.580 (3.76);7.567 (3.55); 7.436 (0.98); 5.824 (0.61); 3.338 (5.11); 2.673(0.37); 2.508 (44.55); 2.504 (58.18); 2.500 (44.49); 2.331(0.39); 1.869 (4.38); 0.008 (2.46); ?0.000 (60.03); ?0.007(3.70). |