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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.
Synonyms: p-Cyanobenzylamine hydrochloride; 4-(Aminomethyl)benzonitrile hydrochloride
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CAS No. : | 15996-76-6 |
Formula : | C8H9ClN2 |
M.W : | 168.62 |
SMILES Code : | [H+].C1=C(C=CC(=C1)CN)C#N.[Cl-] |
Synonyms : |
p-Cyanobenzylamine hydrochloride; 4-(Aminomethyl)benzonitrile hydrochloride
|
MDL No. : | MFCD01861472 |
InChI Key : | QREZLLYPLRPULF-UHFFFAOYSA-N |
Pubchem ID : | 9942250 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.5% | Triethylamine (4.932 mL, 35.583 mmol) was added to solution of 4-(aminomethyl)benzonitrile hydrochloride (5.000 g, 29.652 mmol) in dichloromethane (20 mL) at the room temperature, and the mixture was stirred for 10 mm at the same temperature. The reaction mixture was treated at the same temperature with Di-tert-butyl dicarbonate (6.795 g, 31.135 mmol) and stuffed for additional 5 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The title compound was used without further purification (tert-butyl (4-cyanobenzyl)carbamate, 6.850 g, 99.5 %, whtie solid). | |
95% | With triethylamine; In dichloromethane; at 0 - 20℃; for 16h; | 4-(Aminomethyl)benzonitrile hydrochloride 1 (2.82 g, 16.7 mmol) and triethylamine (4.7 mL, 33.7 mmol) were dissolved in anhydrous CH2C12 (50 mL) at 0 C. To this stirred solution was added di-tert-butyl dicarbonate (4.38 g, 20.1 mmol), and the reaction allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was evaporated in vacuo, and the residue was redissolved in diethyl ether (50 mL), which was washed successively with 0.5 M aq. HC1 (2 x 25 mL), saturated NaHCO3 (2 x 25 mL) and brine (25 mL). The organic layer was dried with Mg504, filtered and evaporated in vacuo to give an off-white solid. The residue was purified by flash column chromatography (Hexanes/EtOAc = 10/1) to afford tert-butyl (4- cyanobenzyl) carbamate 2 (3.69 g, yield 95 %) as a colorless solid. It was further characterized according to the literature procedure (4). Figures ]3A-]3B show ?H-NMR and ?3C-NMR spectra, respectively. |
94% | With sodium carbonate; In dichloromethane; at 0 - 20℃; | (1) To a solution of 4-aminomethylbenzonitrile hydrochloride (n-1) (5.00 g, 29.7 mmol) in dichloromethane(167 mL), sodium carbonate (7.54 g, 71.2 mmol) was added. The reaction mixture was cooled to 0 C. and di-tert-butyl dicarbonate (7.57 mL, 32.6 mmol) was added; the resulting mixture was brought to room temperature at which it was stirred overnight. To the reaction mixture, water was added and extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure and the residue was purified by silica gel (NH) column chromatography (n-hexane:ethyl acetate=1:1) to give tert-butyl 4-cyanobenzylcarbamate (n-2) (amount, 6.48 g; yield, 94%). |
94% | With sodium carbonate; In dichloromethane; at 0 - 20℃; | To a solution of 4-aminomethylbenzonitrile hydrochloride (n-1) (5.00 g, 29.7 mmol) in dichloromethane(167 mL), sodium carbonate (7.54 g, 71.2 mmol) was added. The reaction mixture was cooled to 0C and di-tert-butyl dicarbonate (7.57 mL, 32.6 mmol) was added; the resulting mixture was brought to room temperature at which it was stirred overnight. To the reaction mixture, water was added and extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure and the residue was purified by silica gel (NH) column chromatography (n-hexane:ethyl acetate = 1:1) to give tert-butyl 4-cyanobenzylcarbamate (n-2) (amount, 6.48 g; yield, 94%). |
80% | With sodium hydroxide; In water; for 16h; | Intermediate 28: tert-butyl {4-[amino(hvdroxyirnino)methyllbenzyl}carbamateStep 1: tert-butyl 4-cyanobenzylcarbamate To a solution of 4-cyanobenzylamine hydrochloride (1.05 g; 6.25 mmol) in water (10 mL) was added sodium hydroxide (0.75 g; 18.75 mmol) and di-tert-butyldicarbonate (1 .49 g; 6.87 <n="114"/>mmol) and the mixture was stirred for 16 hours. The solid was collected by filtration and dried in a vacuum oven at 40C for 48 hours. The title compound was isolated as a white solid (1 .35 g; 80%). 1H NMR: (CDCI3, 400MHz) delta 7.62 (2H, d, J = 8.1 Hz), 7.39 (2H, d, J = 8.0 Hz), 4.97 (1 H, s), 4.37 (2H, d, J = 6.2 Hz), 1.46 (9H, s). |
With sodium hydroxide; In 1,4-dioxane; water; at 0℃; for 4.16667h; | 100 g (0.593 mol) of 4-cyanobenzylamine×HCl were dissolved in 1.2 l of dioxane and 600 ml of 2 N NaOH. 142.3 g (0.652 mol) of di(tert-butyl)pyrocarbonates were added in two portions over 10 min at 0 C. The pH was adjusted to 9-10 by adding 2 N NaOH, and the mixture was stirred for a further 4 h. The solvent was removed in vacuo, and the residue was taken up with ethyl acetate, washed 3× each with 5% KHSO4 and NaCl-saturated water and then dried over Na2SO4. The solvent was removed in vacuo (white solid). Yield: 132.6 g (0.57 mol) of white solid, HPLC: 51.6% B | |
With triethylamine; In dichloromethane; | Synthesis of tert-butyl(4-cyanobenzyl)carbamate (7) (0149) 4-Cyanobenzylamine HCl (5.00 g, 29.7 mmol, 1.0 eq) was suspended in CH2Cl2 and NEt3 (10.3 mL, 74.1 mmol, 2.5 eq) were added to obtain a clear solution. Boc2O (8.86 mL, 38.6 mmol, 1.3 eq) was added and the solution was stirred overnight. The reaction mixture was diluted to a total volume of 100 mL with CH2Cl2 and washed with 1 M HCl (3×15 mL) and sat. NaHCO3 (3×15 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure. (0150) 1H NMR (500 MHz, CDCl3) delta 7.58-7.52 (m, 2H), 7.35-7.29 (m, 2H), 4.88 (s, 1H), 4.30 (d, J=6.3 Hz, 2H), 1.39 (s, 9H). (0151) 13C NMR (126 MHz, CDCl3) delta 156.2, 145.0, 132.8, 128.2, 119.1, 111.6, 80.5, 44.6, 28.8. (0152) HRMS (ESI): m/z calc. for C13H16N2NaO2+: 255.1104. found: 255.1110 (Delta=-2.0 ppm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With DIEA; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; | Preparation 15 Synthesis of (S)-4-tert-butoxycarbonylamino-4-(4-cyano-benzylcarbamoyl)-butyric acid benzyl ester (Q) A solution of <strong>[117997-81-6]Boc-Glu(OBzl)-OH</strong> (7.08 g, 21.0 mmol), BOP (9.72 g, 22.0 mmol) and DIEA (12.18 ml, 70.0 mmol) in DMF (50 ml) was maintained at room temperature for 20 min, followed by the addition of 4-(aminomethyl)benzonitrile hydrochloride (3.38 g, 20.0 mmol). The reaction mixture was stirred at room temperature for an additional 1 h and diluted with EtOAc (500 ml). The obtained solution was extracted with water (100 ml), 5% aq. NaHCO3 (100 ml) and water (2*100 ml). The organic layer was dried over MgSO4, evaporated and dried in vacuo to provide compound Q (9.65 g, yield exceeded quantitative) as yellowish oil. LC-MS [M+H] 452.0 (C25H29N3O5+H, calc: 452.4). | |
With DIEA; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; | Preparation 15 Synthesis of (S)-4-tert-butoxycarbonylamino-4-(4-cyano-benzylcarbamoyl)-butyric acid benzyl ester (Q) A solution of <strong>[117997-81-6]Boc-Glu(OBzl)-OH</strong> (7.08 g, 21.0 mmol), BOP (9.72 g, 22.0 mmol) and DIEA (12.18 mL, 70.0 mmol) in DMF (50 mL) was maintained at room temperature for 20 min, followed by the addition of 4-(aminomethyl)benzonitrile hydrochloride (3.38 g, 20.0 mmol). The reaction mixture was stirred at room temperature for an additional 1 h and diluted with EtOAc (500 mL). The obtained solution was extracted with water (100 mL), 5% aq. NaHCO3 (100 mL) and water (2*100 mL). The organic layer was dried over MgSO4, evaporated and dried in vacuo to provide compound Q (9.65 g, yield exceeded quantitative) as yellowish oil. LC-MS [M+H] 452.0 (C25H29N3O5+H, calc: 452.4). |
Tags: 4-(Aminomethyl)benzonitrile HCl | p-Cyanobenzylamine hydrochloride | Nitriles | Amines | Aryls | Inorganic Salts | Fluorinated Building Blocks | Synthetic Reagents | Organic Building Blocks | 15996-76-6
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