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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.
tert-Butyl (3-aminopropyl)carbamate is a carbamate derivative with a tert-butyl group. It is used as a protecting group in organic synthesis.
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CAS No. : | 75178-96-0 |
Formula : | C8H18N2O2 |
M.W : | 174.24 |
SMILES Code : | NCCCNC(OC(C)(C)C)=O |
MDL No. : | MFCD00210021 |
InChI Key : | POHWAQLZBIMPRN-UHFFFAOYSA-N |
Pubchem ID : | 2735700 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P261-P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 2735 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
General procedure: Tert-butyl (5-aminoethyl)carbamate (11.7 g) was dissolved in THF (110 mL), and then Et3N (16 mL, 3.0 equiv) was added to the solution under stirring. The mixture was kept at room temperature (rt) for 10 min. Ethyl bromoacetate (12.24 mL, 1 equiv) was dissolved in THF (100 mL) and added dropwise to the solution under stirring. The mixture was kept at rt for 16 h. The mixture was concentrated in vacuo, and then the residue redissolved in Et2O (300 mL) and filtered. The filtrate was concentrated in vacuo to afford the intermediate ethyl ester (17.65 g) as a colourless oil, which was dissolved in dioxane (100 mL) and MeOH (40 mL). Then, 4M NaOH (18 mL) was added dropwise under stirring. The mixture was kept at rt for 1 h, then concentrated in vacuo, and the residue redissolved in H2O (100 mL). Fmoc-OSu (23.69 g, 1 equiv) was dissolved in warm (45 C) MeCN (170 mL) and added dropwise to the mixture under stirring. The mixture was kept at rt for 16 h, then concentrated in vacuo until it turned turbid. Then EtOAc (300 mL) was added, and the resulting mixture was washed with 10% citric acid (400 mL). The aqueous phase was extracted with EtOAc (2 × 150 mL), and the combined organic phases were washed with H2O (3 × 250 mL), and brine (250 mL). The organic phase was extracted with 10% NaHCO3-10% Na2CO3-dioxane 3:3:2 (4 × 400 mL). The combined aqueous phases were adjusted to pH 2-3 with 4M HCl, extracted with EtOAc (150 mL), then combined, dried over Na2SO4and concentrated in vacuo. The resulting solid was recrystallised from EtOAc (200 mL) and heptane (800 mL) to afford building block17(25.0 g, 77.6%) as a white solid; tR= 6.53 min. (gradient 30-100% B during 10 min). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2h; | General procedure: The mono Boc-protected diamines (1eq.) in DMF were added potassium carbonate (2eq.) and intermediates 2 or 3 (2eq). The mixture was heated at 120 oC for 2h. After cooling, the solution was taken up in ethyl acetate and washed with 1M HCl,1 M NaHCO3 and brine each for twice. The organic layer was dried and evaporated to give the crude final product. The product compound 5 was purified by silica gel column chromatography using PE-EA as an eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 2.0h; | General procedure: The mono Boc-protected diamines (1eq.) in DMF were added potassium carbonate (2eq.) and intermediates 2 or 3 (2eq). The mixture was heated at 120 oC for 2h. After cooling, the solution was taken up in ethyl acetate and washed with 1M HCl,1 M NaHCO3 and brine each for twice. The organic layer was dried and evaporated to give the crude final product. The product compound 5 was purified by silica gel column chromatography using PE-EA as an eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V); In dichloromethane; for 16h; | Step 1 : To slurry of 5-amino-lH-pyrazole-3-carboxylic acid (0.318 g, 2.5 mmol), tert-butyl 3-aminopropylcarbamate (0.479 g, 2.75 mmol) and Hunig'sBase (2.183 mL, 12.50 mmol) in CH2C12 (8 mL) was added PyBOP (1.561 g, 3.00 mmol) and tin- resulting solution was stirred for 16 h. After concentration, the residue was purified by Biotage eluting with 5%-20% MeOH in CH2C12 to give 700 mg of a crude product that will be used as it is in the next step. MS m/z (M+H) + 284.10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With dicyclohexyl-carbodiimide; In dichloromethane; at 20 - 25℃; for 18h; | A solution of 3-BOC-aminopropylamine (3.22 g; 18 mmol) in CH2Cl2 (10 mL) is added dropwise to a stirred suspension of (R)(-) ibuprofen (3 g; 17.5 mmol), DCC (3.8 g; 18 mmol) and HOBZ (2.8 g; 18 mmol) in CH2Cl2 (50 mL) at 25°C. The stirring is continued for 18 hrs at r. t.; after DCU removal by filtration, the reaction mixture is evaporated to dryness in vacuum. The residue oil is more times taken up with acetonitrile; finally the collected extracts are filtered, evaporated to dryness to give a crude sample of (R) 2-(4-isobutylphenyl)-N-3-(BOC-aminopropyl)propionamide that is crystallized from hot MeOH (50 mL) to obtain 3.4 g (9.25 mmol,. 53percent yield) of pure (R) 2-(4-isobutylphenyl)-N-3-(BOC-aminopropyl)propionamide by cooling at T= +4°C for 18 hrs |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With sodium cyanoborohydride; acetic acid; In ethanol; at 60℃; | 6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-one (1.0 g, 3.79 mmol), N-boc propylenediamine (1.98 g, 11.37 mmol) and sodium cyanoborohydride (1.19 g, 18.95 mmol) were dissolved inethanol (20 mL). Catalytic amount of acetic acid was added. The reaction mixture was stirred for overnight at 60 C. After removal of solvent, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with 10% sodium hydroxide and brine, and it was dried over sodium sulfate. The organic layer was concentrated under reduced pressure. The residue was purified on an ISCO chromatograph (0-100% ethyl acetate/hexane) to give the product as awhite solid (1.58 g, 99%);?HNMR (300 IVIHz) (CDC13) 9.47 (bs, 1H), 7.62 (s, 1H), 7.3 1-7.26 (m, 2H). 5.15 (bs, 1H), 5.02 (bs, 1H), 4.59-4.55 (m, 1H), 3.31-3.04 (m, ), 2.77-2.65 (m, 4H), 2.77-2.65 (m, 2H), 2.22-1.91 (m, 6H), 1.33 (s, 9H); LC/MS RT = 3.02 (M+W: 422/424). |
73% | 6-Bromo-2,3,4,9-tetrahydro-1H-indazole-1-one (4.0 mmol, 1056 mg) was added to 15 mL of toluene and then N-Boc-1,3-propanediamine was added (8.0mmol, 1.4mL) and catalytic amount of p-toluenesulfonic acid, add water separator and reflux at 140C for 16h,Then, the solvent was removed by distillation, the solvent was removed, 20 mL of methanol was added, NaBH 4 (20 mmol, 757 mg) was added in portions at room temperature, and the mixture was refluxed for 4 h. The reaction was completely monitored by TLC. The reaction was quenched with a small amount of water, and the solvent was removed by distillation under reduced pressure. EA, H 2 O system was used. Extraction, washing with saturated brine, drying over anhydrous Na2SO4, column chromatography to give an intermediateN1-(6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl)-N3-Boc-1,3-propanediamine(1.237 g, yield 73%). | |
General procedure: To a solution of 1,2-cyclohexanedione (2243?mg, 20?mmol) and concentrated hydrochloric acid (13?mL) in acetic acid (40?mL), p-tolylhydrazine hydrochloride (1586?mg, 10?mmol) in methanol (25?mL) was added dropwise slowly over 10?min. After the addition, the resulting mixture was heated to 60?C, and stirred overnight. The solvent was evaporated, and the residue was pH adjusted to weak alkaline with saturated NaHCO3. The mixture was extracted with AcOEt (3?*?20?mL). The combined organic extract was washed with brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel chromatography (petroleum ether/AcOEt, 12/1 v/v) to give intermediate 7 (1235?mg, 62%) as a brown powder. The mixture of intermediate 7 (102?mg, 0.5?mmol), 4-phenylbutylamine (0.12?mL, 0.8?mmol) and catalytic p-TsOH in toluene (10?mL) was refluxed at 140?C for 16?h with a Dean-Stark trap in place. The solvent was evaporated and the residue was dissolved in methanol. NaBH4 (177?mg) was then added at 0?C. The solution was heated to 80?C until TLC indicated the reaction was complete. The reaction was quenched with water and concentrated. Subsequently, the mixture was extracted with AcOEt twice and the combined organic layers were dried over anhydrous Na2SO4. After evaporation of the solvent, the resulting residue was purified by column chromatography on silica gel (petroleum ether/AcOEt, 4/1 v/v) to give compound 5 (123?mg, Yield: 72%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a solution of 1,2-cyclohexanedione (2243?mg, 20?mmol) and concentrated hydrochloric acid (13?mL) in acetic acid (40?mL), p-tolylhydrazine hydrochloride (1586?mg, 10?mmol) in methanol (25?mL) was added dropwise slowly over 10?min. After the addition, the resulting mixture was heated to 60?C, and stirred overnight. The solvent was evaporated, and the residue was pH adjusted to weak alkaline with saturated NaHCO3. The mixture was extracted with AcOEt (3?*?20?mL). The combined organic extract was washed with brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by silica gel chromatography (petroleum ether/AcOEt, 12/1 v/v) to give intermediate 7 (1235?mg, 62%) as a brown powder. The mixture of intermediate 7 (102?mg, 0.5?mmol), 4-phenylbutylamine (0.12?mL, 0.8?mmol) and catalytic p-TsOH in toluene (10?mL) was refluxed at 140?C for 16?h with a Dean-Stark trap in place. The solvent was evaporated and the residue was dissolved in methanol. NaBH4 (177?mg) was then added at 0?C. The solution was heated to 80?C until TLC indicated the reaction was complete. The reaction was quenched with water and concentrated. Subsequently, the mixture was extracted with AcOEt twice and the combined organic layers were dried over anhydrous Na2SO4. After evaporation of the solvent, the resulting residue was purified by column chromatography on silica gel (petroleum ether/AcOEt, 4/1 v/v) to give compound 5 (123?mg, Yield: 72%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With triethylamine; In tetrahydrofuran; at 20℃; for 18h;Inert atmosphere; | General procedure: the coupling of substituted pyrroles with amine for synthesis of mono-pyrroleanalogues 27 and 28.To a solution of pyrrole 2 (1 equiv.) in dry THF at r.t., under an atmosphere of nitrogen, amine(1 equiv.) and triethylamine (4 equiv.) was added dropwise. The mixture was stirred for 18-72 h andthe solvent was removed in vacuo to give the crude product which was purified as stated. |