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CAS No. : | 102638-45-9 | MDL No. : | MFCD08275208 |
Formula : | C12H17NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | HALKLPHYNWBHPB-UHFFFAOYSA-N |
M.W : | 207.27 | Pubchem ID : | 19851353 |
Synonyms : |
|
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P261-P264-P270-P272-P280-P301+P310+P330-P302+P352-P333+P313-P363-P405-P501 | UN#: | 3259 |
Hazard Statements: | H302-H312-H315-H318-H332-H335 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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 |
---|---|---|
1,1-Dimethylethyl 3-[(3R,6/?)-3-(2,3-dihydro-1H-inden-2-yl)-6-(1-ethylpropyl)-2,5- dioxo-1-piperazinyl]methyl}benzoate 1 ,1-Dimethylethyl-3-(aminomethyl)benzoate (2.69 g, 12.98 mmol) was dissolved in methanol (15 ml) and 2-ethylbutanal (1.6 ml, 13 mmol) was added followed by (2R)-2,3- dihydro-1/-/-inden-2-yl([(phenylmethyl)oxy]carbonyl}amino)ethanoic acid (4.225 g, 12.99 mmol). The mixture was stirred for 11 minutes before 2-[(phenylmethyl)oxy]phenyl isocyanide (2.73 g, 13 mmol) was added. The mixture was stirred at room temperature for 1.8 hours and then left to stand over the weekend (65 hours) before the solvent was evaporated under reduced pressure to leave a sandy foam. The foam in solution in ethanol (90 ml) containing acetic acid (1.5 ml) was hydrogenated at room temperature and pressure over 10 % Pd/carbon (1.42 g) for 18.5 hours. The reaction was filtered through glass fibre filters and the solvent removed in vacuo to give a pale brown foam. The foam was stirred in chloroform (50 ml) and treated with glacial acetic acid (2ml). The mixture was stirred overnight (21.5 hours) at room temperature. Then the reaction mixture was diluted with chloroform (100 ml) and washed with 2M hydrochloric acid (40 ml) followed by saturated aqueous sodium bicarbonate solution (40 ml). The phases were separated by hydrophobic frit and the organic phase was evaporated under reduced pressure and dried in vacuo to leave a brown solid. The solid was loaded in dichloromethane onto a 12Og flash silica chromatography column (pre-eluted with 10% ethyl acetate in cyclohexane). The column was eluted with 10% to 100% ethyl acetate in cyclohexane to afford 1 ,1-dimethylethyl 3-[(3R,6R)-3-(2,3-(ihydro-'H-nden-2-y)-6-(-- ethylpropyl)-2,5-dioxo-1-piperazinyl]methyl}benzoate as a pale yellow solid (2.115 g). LCMS (A) Rt = 3.77 minutes; m/z [IvRH]+ = 508. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.1% | To the mixture of methyl (R)-3-((1 -ethyl-1 H-1 , 2,3-triazol-4-yl)methoxy)-3-(3-(hydroxymethyl)- 4-methylphenyl)-2,2-dimethylpropanoate (100 mg, 0.277 mmol in dichloromethane (1 ml.) was added SOCI2 (0.101 ml_, 1.383 mmol). The resulting reaction mixture was stirred at ambient temperature for 30 min then was evaporated down under vacuum. The residue was dissolved in acetonitrile (4 mL) after which was added <strong>[102638-45-9]tert-butyl 3-(aminomethyl)benzoate</strong> (86 mg, 0.415 mmol) and DIEA (0.193 mL, 1.107 mmol). The resulting reaction mixture was heated with microwave at 100 C for 1 h after which was added benzenesulfonyl chloride (0.054 mL, 0.415 mmol). The resulting reaction mixture was stirred at ambient temperature for 1 h before was quenched with water (0.2 mL), evaporated down under vacuum, purified via flash chromatography over silica gel to give the title compound (95.7 mg, 0.139 mmol, 50.1 % yield). LC/MS: m/z 691.4 (M+H)+, 1 .47 min (ret. time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
103.6 mg | To the mixture of methyl (R)-3-(3-(chloromethyl)-4-methylphenyl)-2,2-dimethyl-3-((1-propyl- 1 H-1 ,2,3-triazol-4-yl)methoxy)propanoate (90 mg, 0.228 mmol) in acetonitrile (3 ml.) was added tert-butyl 3-(aminomethyl)benzoate (71 .0 mg, 0.343 mmol) and DIEA (0.160 ml_, 0.914 mmol). The resulting reaction mixture was heated with microwave at 100 C for 1 h after which was added methyl 3-(chlorosulfonyl)benzoate (80 mg, 0.343 mmol). The resulting reaction mixture was stirred at ambient temperature for 23 h then was evaporated down under vacuum, purified via flash chromatography over silica gel to give the title compound (103.6 mg, 0.136 mmol, 59.4% yield). LC/MS: m/z 763.5 (M+H)+, 1.48 min (ret. time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formic acid; palladium on activated charcoal; triethylamine; In tetrahydrofuran; at 40℃; for 4h;Inert atmosphere; | A mixture of HCOOH and TEA (25 mL, V:V=5:1) followed by Pd/C (1.1 g) was slowly added to asolution of compound 43a in THF (25 mL) under Ar atmosphere. The mixture was stirred at 40 C for4 h and filtered. The filtrate was neutralized with saturated NaHCO3 and concentrated to remove THF.The residue was extracted with EA. The combined organic layer was washed with saturated NaCl,dried (Na2SO4), and concentrated to give compound 43b. GC-MS m/z 207 [M]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; | Compound 43b (2 mmol), IM (2 mmol), and 4-dimethylaminopyridine (DMAP, 20 mg) wasadded to DCM (20 mL). Then 1-ethyl-(3-dimethylaminopropyl)carbonyldiimide hydrochloride (EDCI,4 mmol) was added. The mixture was stirred at room temperature until the reaction was completed,and concentrated. The residue was purified by column chromatography (PE/EA=4:3, V/V) to give 43cin yield of 68%. 1H-NMR (DMSO-d6): 9.28 (t, J = 6.0 Hz, 1H), 8.02 (d, J = 8.8 Hz, 2H), 7.89 (s, 1H),7.79 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.0 Hz, 1H), 4.55 (d,J = 6.0 Hz, 2H), 4.09 (s, 2H), 3.71 (s, 3H), 1.54 (s, 9H) ppm. |
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