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CAS No. : | 55186-89-5 | MDL No. : | MFCD00225259 |
Formula : | C12H16N2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DKNOPZCYIDBMNY-UHFFFAOYSA-N |
M.W : | 204.27 | Pubchem ID : | 239726 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302+H312+H332-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
47% | [Referential Example 119]; 1-Benzylhexahydro-1H-1,4-diazepin-5-one ; [] Concentrated sulfuric acid (25 mL) was added to 1-benzyl-4-piperidone (10.14 g) in acetic acid (50 mL) at room temperature, and sodium azide (3.880 g) was added thereto at 0C over a period of 2 hours, followed by stirring at 5C for 25 hours. The reaction mixture was alkalinized through addition of aqueous sodium hydroxide, followed by partitioning by use of chloroform. The aqueous layer was extracted with chloroform. The organic layers were combined, and washed with saturated brine, and then dried over sodium sulfate anhydrate, followed by filtration. The solvent was evaporated under reduced pressure, and then the residue was purified through silica gel column chromatography (chloroform - methanol), to thereby give the title compound as a solid (5.081 g, 47%).1H-NMR(400MHz,CDCl3)delta: 2.50-2.70(6H,m), 3.20-3.35(2H,m), 3.60(2H,s), 6.07(1H,br), 7.20-7.40(5H,m). MS(ESI)m/z: 205(M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | Step 2: Synthesis of l-benzyl-l,4-diazepan-5-one [142]To a clean and dried two necked round bottom flask [141] (2 g, 0.00976 mol) was dissolved in acetone (20 ml) and acetonitrile (20 ml). The reaction mixture was cooled to 0 C, and then to it 15 % aqueous NaOH ( 1.2 ml) was added drop wise, followed by the addition of benzene sulphonyl chloride (1.49 ml, 0.01 1 mol). The reaction mixture was refluxed overnight. TLC showed complete consumption of SM. The reaction mixture was diluted with acetone, and passed through celite and concentrated. Saturated NaHC03 (50 ml) was added to the solid followed by extraction with EtOAc (3 X 150 ml), removal of the solvent under reduced pressure. The residue was purified by column chromatograph on silica gel with MeOH:DCM (1%) as an eluent to afford [142] as a white solid (600 mg, 30 %).ESIMS: 205 (M+ + 1) | |
30% | With benzenesulfonyl chloride; sodium hydroxide; In water; acetone; acetonitrile; at 0℃;Reflux; | Step 2 To a clean and dried two necked round bottom flask [110] (2 g, 9.76 mmol) was dissolved in acetone (20 ml) and acetonitrile (20 ml). The reaction mixture was cooled to 0 (>C, and then to it 15 % aqueous NaOH ( 1.2 ml) was added drop wise, followed by the addition of benzene sulphonyl chloride ( 1.49 ml, 1 1 mmol). The reaction mixture was refluxed overnight. TLC showed complete consumption of SM. The reaction mixture was diluted with acetone, and passed through celite and concentrated. Saturated NaHCOj (50 ml) was added to the solid followed by extraction with EtOAc (3 X 150 ml), removal of the solvent under reduced pressure. The residue was purified by column chromatography on silica gel with MeOH: DCM ( 1 ) as an eluent to afford [111] as a white solid (600 mg, 30 ). , ESIMS: 205 (M+ + 1 ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; hydrogen;palladium(II) hydroxide; In methanol; at 45℃;Inert atmosphere; | Step 3: Synthesis of l,4-diazepan-5-one [143]To a clean and dried two-necked RB flask taken compound [142] (600 mg, 2.93 mmol) was dissolved in eOH (15 ml). Concentrated HC1 (0.05 ml) and Pd(OH)2 ( 120 mg) were added sequentially under a nitrogen atmosphere. The reaction mixture was heated to 45 C under a hydrogen atmosphere and maintained at 45 C overnight. The reaction was monitored by mass analysis. Crude compound [143] obtained was used as such for the next step (350 mg, crude). ESIMS: 1 15 (M+ + 1 ) | |
With hydrogenchloride; hydrogen; palladium(II) hydroxide; In methanol; at 45℃;Inert atmosphere; | Step 3 To a clean and dried two-necked RB flask taken compound [111] (600 mg, 2.93 mmol) was dissolved in MeOH (15 ml). Concentrated HCI (0.05 ml) and Pd(OH)2 ( 120 mg) were added to the solution sequentially under a nitrogen atmosphere. The reaction mixture was heated to 45 C under a hydrogen atmosphere and maintained at 45 C overnight. The reaction was monitored by mass analysis. Crude compound [112] obtained was used as such for the next step (350 mg, crude). ESIMS: 1 15 (M+ + 1 ) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 100℃; for 12.0h; | To a solution of 24.6 mmol of 9 and 27.3 mmol of 7 in 50 mL of 1,4-dioxane was added 4.92 mmol of copper (I) iodide followed by the addition of 49.2 mmol of K3P04 and 4.92 mmol of trans-cyclohexanediamine, then the resulting mixture was stirred at 100C for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was diluted with CHC13, poured into water, and insoluble material was removed by celite filtration. The filtrate was extracted with CHC13, dried over MgS04 and concentrated in vacuo. The crude product was purified by column chromatography to give 7.87 mmol of nitro derivative. [0202] A solution of 7.66 mmol of nitro derivative and 0.5 g of Pd/C (10%) in 150 mL of methanol was stirred overnight under H2 (1 atm). After filtering through celite, the solution was concentrated under reduced pressure to give 4.75 mmol of 8. | |
With potassium phosphate;copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 100℃; for 12.0h; | To a solution of 24.6 mmol of 9 and 27.3 mmol of 7 in 50 mL of 1,4-dioxane was added 4.92 mmol of copper (I) iodide followed by the addition of 49.2 mmol ofK3P04 and 4.92 mmol of trans-cyclohexanediamine, then the resulting mixture was stirred at 100C for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was diluted with CHC13, poured into water, and insoluble material was removed by celite filtration. The filtrate was extracted with CHCl3, dried over MgS04 and concentrated in vacuo. The crude product was purified by column chromatography to give 7.87 mmol of nitro derivative. [0233] A solution of 7.66 mmol of nitro derivative and 0.5 g of Pd/C (10%) in 150 mL of methanol was stirred overnight under H2 (1 atm). After filtering through celite, the solution was concentrated under reduced pressure to give 4.75 mmol of 8. 1H NMR (400 MHz, DMSO-d6) 8 7.70 (d, J = 2.4 Hz, 1H), 7.17 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 7.30-7.36 (m, 5H), 6.40 (d, J = 8.8 Hz, 1H), 5.90 (br s, 2H), 3.66-3.72 (m, 2H), 3.59 (br s, 2H), 2.59-2.71 (m, 6H); MS m/z: 327 (M+I). | |
With potassium phosphate; copper(l) iodide; trans-1,2-cyclohexanediamine; In 1,4-dioxane; at 100℃; for 12.0h; | Example 6 Preparation of 8 6.1 Ullmann Cross-Coupling To a solution of 24.6 mmol of 9 and 27.3 mmol of 7 in 50 mL of 1,4-dioxane was added 4.92 mmol of copper (I) iodide followed by the addition of 49.2 mmol of K3PO4 and 4.92 mmol of trans-cyclohexanediamine, then the resulting mixture was stirred at 100 C. for 12 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was diluted with CHCl3, poured into water, and insoluble material was removed by celite filtration. The filtrate was extracted with CHCl3, dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography to give 7.87 mmol of nitro derivative. A solution of 7.66 mmol of nitro derivative and 0.5 g of Pd/C (10%) in 150 mL of methanol was stirred overnight under H2 (1 atm). After filtering through celite, the solution was concentrated under reduced pressure to give 4.75 mmol of 8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogenchloride; hydrogen;palladium 10% on activated carbon; In methanol; ethanol; at 20℃; for 4.0h; | Referential Example 120]; Hexahydro-1H-1,4-diazepin-5-one hydrochloride ; [] 1M HCl in ethanol (7.2 mL) and 10% palladium-carbon (0.34 g) were added to <strong>[55186-89-5]1-benzylhexahydro-1H-1,4-diazepin-5-one</strong> (1.490 g) in methanol (10 mL) at room temperature, and the resultant mixture was stirred in a hydrogen atmosphere for 4 hours. After the reaction atmosphere was purged with nitrogen, insoluble matter was removed by filtration. The solvent of the filtrate was evaporated under reduced pressure, and diethyl ether was added to the residue, and then the precipitated solid was recovered by filtration, to thereby give the title compound (1.045 g, 96%).1H-NMR(400MHz,CD3OD)delta: 2.75-2.85(2H,m), 3.25-3.40(6H,m), 3.48-3.56(2H,m) . MS(ESI)m/z: 115(M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With caesium carbonate;palladium diacetate; In 1,4-dioxane; | Part A. 1-Benzyl-4-(4-bromo-phenyl)-[1,4]diazepan-5-one: Commercially available <strong>[55186-89-5]1-benzyl-(1,4)-diazepan-5-one</strong> (14.7 mmol), p-bromoiodobenzene (1 eq), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.15 eq), cesium carbonate (1.5 eq), and palladium acetate (0.1 eq) were placed in a round bottom flask and it was evacuated and flushed 3* with nitrogen. To this mixture was then added 200 mL of dioxane and the resulting solution was again evacuated and flushed 3* times with nitrogen gas. The mixture was allowed to stir at 75 C. overnight during which time the mixture turned from brown to bright yellow suspension. The mixture was cooled and diluted with dichloromethane and then was filtered through a pad of celite. The filtrate was removed under reduced pressure and the residue was purified by flash column chromatography eluding with 50% EtOAc/Hex to give compound 1 as an off-white solid (63%). Mass spectrum, ESI (M+H) 359.3, 361.3. |
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