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Structure of 5452-35-7
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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. : | 5452-35-7 |
Formula : | C7H15N |
M.W : | 113.20 |
SMILES Code : | NC1CCCCCC1 |
MDL No. : | MFCD00004153 |
InChI Key : | VXVVUHQULXCUPF-UHFFFAOYSA-N |
Pubchem ID : | 2899 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H335 |
Precautionary Statements: | P210-P233-P240-P241+P242+P243-P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P370+P378-P403+P235-P501 |
Class: | 8(3) |
UN#: | 2734 |
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 |
---|---|---|
33% | Example 45 Synthesis of ({4-cycloheptylamino-6-[((S)-1-ethyl-pyrrolidin-2-ylmethyl)-amino]-1,3,5-triazin-2-yl}-phenyl-amino)-acetonitrile (143) To a mixture of cyanuric chloride (0.368 g, 2 mmol) in CH3CN at about -20° C. was added N-phenyl glycinonitrile (0.264 g, 2 mmol) in CH3CN followed by the addition of DIEA (0.35 mL, 2 mmol) and stirred for about 1 hour. The reaction mixture was then stirred at room temperature for about 1 hour. Then, cycloheptylamine (0.25 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at rt. Then, S-(-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography eluding with 96:3:1 methylene chloride:methanol:conc. ammonium hydroxide to yield 143, (0.300 g, 33percent) mp 53-55° C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01 M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 6.9 min, 94.1percent purity; MS (ESI): m/z 449 (M+H, 100), 381 (1.2), 353 (16.2), 226 (19.9), 225 (54.3), 212 (20.5), 177 (18.3), 164 (9.6). | |
33% | To a mixture of cyanuric chloride(0. 368 g, 2 mmol) inCH3CN atabout-20 C was added N-phenyl glycinonitrile (0.264 g, 2 mmol) inCH3CN followed by the addition of DIEA (0.35 mL, 2 mmol) and stirred for about 1 hour. The reaction mixture was then stirred at room temperature for about1 hour. Then, cycloheptylamine (0.25 mL, 2 mmol) and DIEA(0. 35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at rt. Then,S- (-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL,2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography eluting with 96: 3: 1 methylene chloride: methanol:conc. ammonium hydroxide to yield 143, (0.300 g, 33percent) mp53-55 C ; HPLC: Inertsil ODS-3VC18, 40:30 : 30 [KH2P04 (0.01 M, pH 3. 2) : CH30H: CH3CN], 264 nm,Rt 6.9 min, 94.1percent purity; MS (ESI):m/z 449 (M+H, 100), 381 (1.2),353 (16.2), 226 (19.9), 225 (54.3), 212 (20.5), 177 (18. 3), 164 (9.6). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | To a mixture of cyanuric chloride (0.368 g, 2 mmol) in CH3CN at approximately -10 to -20 C. was added 3-fluoro-p-anisidine (0.28 g, 2 mmol) in CH3CN followed by the addition of N,N-diisopropylethylamine (DIEA) (0.35 mL, 2 mmol) and stirred for an hour. The reaction mixture was then allowed to reach room temperature for an hour. The second step was continued without further purification. Cycloheptylamine (0.25 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at rt. The third step was also preceded without any further purification. S-(-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over potassium carbonate, filtered, and concentrated under reduced pressure affording 0.920 g crude material. The crude material was purified by column chromatography to yield a white solid 139 (0.550 g, 60%), mp 75-77 C.; HPLC: Inertsil ODS-3V C18, 40:30:30 [KH2PO4 (0.01M, pH 3.2): CH3OH: CH3CN], 264 nm, Rt 7.9 min, 95.9% purity; MS (ESI): m/z 458 (M+H, 100). | |
60% | To a mixture of cyanuric chloride (0.368 g, 2 mmol) inCH3CN at approximately-10to-20 C was added3-fluoro-p-anisidine (0.28 g, 2 mmol) inCH3CN followed by the additionof N, N diisopropylethylamine (DIEA) (0.35 mL, 2 mmol) and stirred for an hour. The reaction mixture was then allowed to reach room temperature for an hour. The second step was continued without further purification. Cycloheptylamine (0.25 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was stirred overnight at rt. The third step was also preceded without any further purification. S-(-)-2-aminomethyl-N-ethyl pyrrolidine (0.29 mL, 2 mmol) and DIEA (0.35 mL, 2 mmol) were added and the reaction mixture was refluxed overnight. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was separated and dried over potassium carbonate, filtered, and concentrated under reduced pressure affording 0.920 g crude material. The crude material was purified by column chromatography to yield a white solid 139 (0.550 g,60%), mp75-77 C ; HPLC: Inertsil ODS-3V C18,40 : 30: 30[KH2P04(O. 01M, pH 3.2) :CH30H :CH3CN], 264 nm, Rt 7.9 min, 95.9% purity; MS (ESI):rnlz 458(M+H, 100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.4% | With pyridine; In methanol; at 140℃; for 0.5h;Microwave irradiation; | General procedure: The starting compound (1.27 mmol) was treated with 18 aliphatic amines, alicyclic amines or saturated heterocycles containing at least one nitrogen atom (2.54 mmol). Four reactions were completed by conventional heating methods. The conditions were 110 C, toluene as a solvent and pyridine (1.27 mmol) as a base. The reaction time was set to one hour. Then the reactions were completed using the microwave reactor with focused field and conditions used for syntheses were 140 C, 30 min,120 W, methanol used as a solvent and pyridine (1.27 mmol) as a base. They were set experimentally with respect to prior experience. The progress of reaction was monitored with TLC in system hexane/ethyl acetate (1:1). Then the mixture was separated by flash column chromatograph using gradient elution. Mobile phases were hexane and ethyl acetate again. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In ethanol; | General procedure: To a solution fo <strong>[579514-75-3]tert-butyl 4-fluoro-3-nitrobenzoate</strong> (560 mg, 2.3 mmol) in 20mL of EtOH were added butan-1-amine (853 mg, 11.6 mmol) and stirred at rt for 2 h.The reaction mixture was concentrated to dryness, and the residue was dissolved inEtOAc (10 x 3 mL) and washed with brine (10 mL). The combined organic layerswere dried over MgSO4, and concentrated in vacuo to afford the product tert-butyl 4-(butylamino)-3-nitrobenzoate (35b) as yellow-orange solid (490 g, 72% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26 mg | The compound represented by the chemical formula (1) was obtained by the following procedure.34.5 mg (0.30 mmol) of cycloheptylamine was dissolved in 1 mL of methylene chloride,42 mg (0.18 mmol) of N-methyl-D-valine (Boc-N-Me-D-Val) having N terminal protected with Boc group, 54 mg (0.28 mmol) of EDCI · HCl, 36.5 mg mmol) were sequentially added, and finally 1 mL of dichloromethane was added and the mixture was stirred at room temperature for 4 hours.The reaction solvent was distilled off under reduced pressure, 20 mL of 1 M hydrochloric acid and 20 mL of ethyl acetate were added,Extraction was then carried out with ethyl acetate (2 × 20 mL).The organic layer was washed with 5% aqueous solution of sodium bicarbonate (20 mL)The organic layer was further dried with brine (20 mL), dried over anhydrous sodium sulfate, the desiccant was filtered, and the filtrate was concentrated under reduced pressure.And further dried with a vacuum pump to obtain a yellow oilDipeptide 1(30 mg, yield 51%).Next, 30 mg (0.092 mmol) of dipeptide 1 was dissolved in 2 mL of a 4 M hydrochloric acid / dioxane solution, stirred at room temperature for 3 hours, and the solvent was distilled off under reduced pressure to obtain a white powder from which the Boc group was removed.This white powder was dissolved in 1.0 mL of methylene chloride, and 39 mg (0.30 mmol) of diisopropylethylamine, 157 mg (0.30 mmol) of PyBOP,9-decenoic acid 17 mg (0.10 mmol) were sequentially added,Finally, 1 mL of dichloromethane was added and the mixture was stirred at room temperature for 14 hours.The reaction solvent was distilled off under reduced pressure, and 20 mL of 1 M hydrochloric acid and 20 mL of ethyl acetate were added for extraction.Further, the reaction solvent was distilled off under reduced pressure, 20 mL of 1 M hydrochloric acid and 20 mL of ethyl acetate were added, followed by extraction with ethyl acetate (2 × 20 mL).The organic layer was washed with 5% aqueous solution of sodium bicarbonate (20 mL), and the organic layer was further dried with brine (20 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was distilled off under reduced pressure It was. Then, the remaining material was isolated and purified by silica gel chromatography (ethyl acetate: n-hexane = 4: 6) to obtain a compound represented by the chemical formula (1).(HPLC) [Inertsil, 250 × 20 mm, solvent ethyl acetate: n-hexane = 3: 7, flow rate: 2.0 mL / min (light yellow oil: 26 mg, yield 74% |