Structure of 134575-12-5
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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. : | 134575-12-5 |
Formula : | C11H20N2O2 |
M.W : | 212.29 |
SMILES Code : | O=C(OC(C)(C)C)NC[C@H]1[C@]2([H])CNC[C@]12[H] |
MDL No. : | MFCD14581078 |
InChI Key : | JXWGBEYMMHSBFU-JVHMLUBASA-N |
Pubchem ID : | 15713440 |
GHS Pictogram: |
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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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium dihydroxide; In methanol; under 1034.32 Torr; for 10.0h; | Step 5: The carbamate (i) (1.9 g, 6.3 mmol) prepared in step 4 wasdissolved in methanol (100 ml) and mixed with palladium hydroxide (20%, 0.4 g).The mixture was transferred to a Parr bottle, which was then charged withhydrogen to a pressure of 20 psi. The Parr bottle was shaken for 10 h. Theremaining hydrogen was removed from the Parr bottle under vacuum, and thereaction was filtered through Celite (diatomaceous earth). The filtrate was thenconcentrated to provide pure amine B (1.4 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 16.0h; | Step 2: A solution of amine B (0.3 g, 1.4 mmol) and triethylamine (0.99 ml_,7 mmol) in CH2CI2 (30 ml) at room temperature was treated with the indolesulfonyl chloride (5a) prepared in step 1 (0.5 g, 1.55 mmol). The mixture wasstirred for 16 h and then diluted with CH2CI2 (100 ml_) and washed once withwater (50 ml_) and twice with brine (50 ml_ each wash). The organic phase wasseparated, dried (Na2SO4) and concentrated to yield a crude product which waspurified by silica-gel chromatography using 1:1 ethyl acetate:hexane as the elutingsolvent. The appropriate fractions were collected and combined, and the solventwas removed under vacuum to provide pure product (5b) (0.46 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 10.0h; | Step 4: A solution of amine B (0.17g, 0.8 mmol) and triethylamine (0.55mL, 3.94 mmol) in methylene chloride (25 mL) was treated with the sulfonylchloride (7c) (0.28 g, 0.78 mmol) prepared in step 3. The reaction mixture wasstirred at room temperature for 10 h, diluted with methylene chloride (50 mL) andwashed sequentially with aqueous NaHCOs (50 mL), water (two aliquots of 50 mLeach), and brine (50 mL). The organic phase was dried and concentrated to yielda crude product. The crude product was purified by preparative plate silica gelchromatography using 1:2 ethyl actetate:hexane as the eluting solvent, therebyproviding 0.26 g of pure product (7d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 5.0h; | Step 4: A solution of amine B (0.06 g, 0.283 mmol) and triethylamine (0.3ml_, 1.4 mmol) in methylene chloride (25 ml_) was treated with the sulfonylchloride (3c) prepared in step 3. The mixture was stirred at room temperature for5 h. The reaction mixture was then diluted with methylene chloride (50 ml_) andwashed sequentially with aqueous NaHCO3 (50 ml), water (two aliquots of 50 ml_each), and brine (50 ml_). The organic phases were separated, dried, andconcentrated to yield a crude product (3d), which was purified by preparative platesilica gel chromatography using 1:2 ethyl actetate:hexane as the eluting solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | 8. [1alpha,5alpha,6alpha]-6-(tert-Butoxycarbonyl)aminomethyl-3-azabicyclo[3.1.0]hexane A mixture of the title compound of Preparation E.7. (240 mg, 0.79 mmol), 10% palladium on carbon (240 mg) and ammonium formate (240 mg, 3.8 mmol) in ethanol (10 ml) was stirred at room temperature for 0.5 hour. The mixture was filtered and concentrated to give a gummy solid which was mixed with methylene chloride and filtered. Removal of solvents under reduced pressure gave a yellow oil which was crystallized from ethyl ether to give the title product as a white solid, mp 95-97 (148 mg, 0.70 mmol, 89% yield). 1H NMR (CDCl3): 8.47 (bs, 1H), 4.80 (bs, 1H), 3.33 (m, 4H), 3.06 (m, 2H), 1.66 (bs, 2H), 1.43 (s, 9H), 1.23 (bs, 1H). | |
With palladium 10% on activated carbon; hydrogen; In methanol; ethyl acetate; at 20℃; under 760.051 Torr; for 3.0h; | General procedure: Benzyl cis-4-(((tert-butoxycarbonyl)amino)methyl)-3-hydroxypiperidine-1- carboxylate (501 mg, 1.375 mmol) was dissolved in MeOH (10 mL) and EtOAc (3 mL), followed by the addition of 10% Pd-C (345 mg, 3.24 mmol). The mixture was stirred at RT under 1 atmosphere of H2 (balloon) for 3 hours. The reaction mixture was filtered and the filter cake was washed with EtOAc and MeOH. The filtrates were concentrated to give the title compound. LC/MS [M+H]+: 231.28 |