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CAS No. : | 89711-08-0 | MDL No. : | MFCD01321273 |
Formula : | C7H13NO3 | Boiling Point : | - |
Linear Structure Formula : | (CH3)3COCONHCH2CHO | InChI Key : | ACNRTYKOPZDRCO-UHFFFAOYSA-N |
M.W : | 159.18 | Pubchem ID : | 4247255 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
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 |
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In methanol; for 0.5h;Product distribution / selectivity; | 4 mmol C-Thiophen-3-yl-methylamine and 1 mmol (2-Oxo-ethyl)-carbamic acid tert-butyl ester were added in 5 ml MeOH (dry). After 30 min the 1 mmol 2-Chloro-4-fluoro-1-[isocyano-(toluene-4-sulfonyl)-methyl]-benzene was added. The reaction was heated to 40 C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods.; C-<strong>[27757-86-4]thiophen-3-yl-methylamine</strong> (4 mmol) and (2-oxo-ethyl)-carbamic acid tert-butyl ester (1 mmol) were added to methanol (5 ml, dry). After 30 min 2,4-dichloro-1-[isocyano-(toluene-4-sulfonyl)-methyl]-benzene (1 mmol) was added. The reaction was heated to 40 C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods. |
Yield | Reaction Conditions | Operation in experiment |
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A solution of the aldehyde A1IJl g, 18.85 mmol) in MeOH (20 ml) was treated with ethylamine (10.37 ml, 20.73 mmol) and stirred at RT for 5 min. The mixture was treated with sodium borohydride (0.856 g, 22.62 mmol). After stirring for 5 min, the mixture was quenched with water and concentrated. The residue was diluted with water, saturated with NaCl, and extracted twice with THF. The organic phase was dried over Na2SO4, filtered and concentrated to yield A-2 as a colorless cloudy oil. |
Yield | Reaction Conditions | Operation in experiment |
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With borane pyridine; acetic acid; In methanol; | 100 mg (0.76 mmol) of commercially available <strong>[2480-23-1]N-methyl-L-valine</strong> and 182 mg (1.14 mmol) of commercially available tert-butyl 2-oxoethyl carbamate were combined in 20 ml of methanol and admixed with 340 mg (3.66 mmol) of borane-pyridine complex and 65 μl of acetic acid. The reaction mixture was stirred at RT overnight. This was followed by concentration under reduced pressure, and the residue was purified by flash chromatography on silica gel with dichloromethane/methanol/17% aqueous ammonia solution (1540.5) as the eluent. After concentration of the corresponding fractions and lyophilization from 1:1 dioxane/ water, 190 mg in 39% purity (35% of theory) of the intermediate were obtained, which were converted further without further purification. [2411] 50 mg (0.07 mmol) of this intermediate were dissolved in 10 ml of DMF and admixed with 52 mg (0.07 mmol) of N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-[(2S)-3-(1H-indol-3-yl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (Intermediate 220), 32 mg (0.09 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) and 37 μl (0.2 mmol) of N,N-diisopropylethylamine. The mixture was stirred at RT overnight and then concentrated. The residue was taken up in ethyl acetate and extracted by shaking first with 5% aqueous citric acid solution and then with water. The organic phase was concentrated and the residue was purified by means of preparative HPLC. The corresponding fractions were combined and the solvent was removed under reduced pressure. After lyophilization from dioxane, 53 mg (76% of theory) of the protected intermediate were obtained. [2412] HPLC (Method 12): Rt=2.0 min; [2413] LC-MS (Method 1): Rt=1.02 min; MS (ESIpos): m/z=984 (M+H)+. [2414] 53 mg (0.05 mmol) of this intermediate were taken up in 10 ml of dichloromethane, 2 ml of trifluoroacetic acid were added, and the reaction mixture was stirred at RT for 30 min Subsequently, the reaction mixture was concentrated under reduced pressure and the remaining residue was purified by means of preparative HPLC. The corresponding fractions were combined, the solvent was removed under reduced pressure and the residue was lyophilized from dioxane/water. In this way, 21 mg (40% of theory) of the title compound were obtained in 65% purity. [2415] HPLC (Method 12): Rt=1.7 min; [2416] LC-MS (Method 1): Rt=0.87 min; MS (ESIpos): m/z=884 (M+H)+. | |
With borane-pyridine complex; acetic acid; In methanol; at 20℃; | [4793] 100 mg (0.76 mmol) of commercially available<strong>[2480-23-1]N-methyl-L-valine</strong> and 182 mg (1.14 mmol) of commerciallyavailable tert-butyl 2-oxoethyl carbamate were combined in20 ml of methanol and admixed with 340 mg (3.66 mmol) ofborane-pyridine complex and 65 fll of acetic acid. The reactionmixture was stirred at RT overnight. This was followedby concentration under reduced pressure, and the residue wasSep.3,2015purified by flash chromatography on silica gel with dichloromethane/methanol/17% aqueous ammonia solution (15/4/0.5) as the eluent. After concentration of the correspondingfractions and lyophilization from 1: 1 dioxane/water, 190 mgin 39% purity (35% of theory) of the intermediate wereobtained, which were converted further without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Methyl 3-((2-((tert-butoxycarbonyl)amino)ethyl)amino)-4-fluorobenzoate (I-44)Methyl 3-amino-4-fluorobenzoate (8.4 mmol) and tert-butyl (2-oxoethyl)carbamate (12.6 mmol) were dissolved in MeOH (100 ml_) and AcOH (10 ml_). After stirring for 1 hr at room temperature the reaction mixture was treated with NaCNBH3(16.6 mmol) and stirred for 2 hrs. After removal of solvent (aspirator) the mixture was dissolved in EtOAc and washed with NaHC03(sat., 1x). The aqueous phase was washed with EtOAc (1x) and the combined organic layers were dried (MgSO^. The product (I-44) was taken on crude for the next step. 1H NMR (400 MHz, CDCl3): delta 7.40-7.38 (m, 2H), 7.02 (dd, J = 8.8 Hz, 11 .1 , 1 H), 4.88 (s, 1 H), 3.91 (s, 3H), 3.40-3.38 (m, 4H), 1.47 (s, 9H). MS (m/z): 313.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Potassium hydroxide (73.9 mg, 1.3 177 mmol%) and tert-butyl N-[(2R)-2-bromopropyl]carbamate (230.1mg, 0.96634 mmol) are added to a solution of <strong>[89830-98-8]4-cyclopropyl-1H-imidazole</strong> (100 mg, 0.087849 mmol) in DMSO (2 mL) at 0 C. The mixture is stirred at room temperature for 65 hours. The reaction is quenched with water and extracted with EtOAc (3x). The organic extracts are washed with saturated NaC1 (3x), dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified bysilica gel flash chromatography with 4% MeOH in DCM to give the title compounds as a mixture of 2 regioisomers (112 mg, 22.82%) and as a yellow oil. ES/MS (m/z): 266 (M+ 1). TFA (2 mL, 26.45 mmol) is added to racemic tert-butyl N-[2-(4-cyclopropylimidazol- i-yl)-i -methyl-ethyl] carbamate and to racemic tert-butyl N- [2-(5 -cyclopropylimidazol-1-yl)-1-methyl-ethyl]carbamate (112 mg, 0.2005 mmol) in DCM(10 mL) at room temperature. The mixture is stirred at room temperature for 1 hour andis concentrated to give the crude title compounds as a mixture of regioisomers (69.8 mg,100%) as a yellow oil. ES/MS (m/z): 166 (M+1). Sodium triacetoxyborohydride (56.9 mg, 0.260 mmol) is added to a solution of racemi c-i -(4-cyclopropylimidazol -1 -yl)propan-2-amine and racemic- 1 -(5- cyclopropylimidazol- 1 -yl)propan-2-amine (69.7 mg, 0.200 mmol) and tert-butyl N-(2- oxoethyl)carbamate (33.6 mg, 0.200 mmol) in DCM (5 mL) and acetic acid (15.6 mg, 0.260 mmol) at room temperature. The mixture is stirred at room temperature for 18 hours. The reaction is quenched by the addition of saturated NaHCO3. The mixture is extracted with DCM (3x), the organic extracts are dried over Na2SO4, filtered, and concentrated to give the crude title compound as a mixture of regioisomers (130 mg, 100%) as a yellow oil. ES/MS (m/z): 309 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Potassium hydroxide (73.9 mg, 1.3 177 mmol%) and tert-butyl N-[(2R)-2-bromopropyl]carbamate (230.1mg, 0.96634 mmol) are added to a solution of <strong>[89830-98-8]4-cyclopropyl-1H-imidazole</strong> (100 mg, 0.087849 mmol) in DMSO (2 mL) at 0 C. The mixture is stirred at room temperature for 65 hours. The reaction is quenched with water and extracted with EtOAc (3x). The organic extracts are washed with saturated NaC1 (3x), dried over Na2SO4, filtered, and concentrated to dryness. The residue is purified bysilica gel flash chromatography with 4% MeOH in DCM to give the title compounds as a mixture of 2 regioisomers (112 mg, 22.82%) and as a yellow oil. ES/MS (m/z): 266 (M+ 1). TFA (2 mL, 26.45 mmol) is added to racemic tert-butyl N-[2-(4-cyclopropylimidazol- i-yl)-i -methyl-ethyl] carbamate and to racemic tert-butyl N- [2-(5 -cyclopropylimidazol-1-yl)-1-methyl-ethyl]carbamate (112 mg, 0.2005 mmol) in DCM(10 mL) at room temperature. The mixture is stirred at room temperature for 1 hour andis concentrated to give the crude title compounds as a mixture of regioisomers (69.8 mg,100%) as a yellow oil. ES/MS (m/z): 166 (M+1). Sodium triacetoxyborohydride (56.9 mg, 0.260 mmol) is added to a solution of racemi c-i -(4-cyclopropylimidazol -1 -yl)propan-2-amine and racemic- 1 -(5- cyclopropylimidazol- 1 -yl)propan-2-amine (69.7 mg, 0.200 mmol) and tert-butyl N-(2- oxoethyl)carbamate (33.6 mg, 0.200 mmol) in DCM (5 mL) and acetic acid (15.6 mg, 0.260 mmol) at room temperature. The mixture is stirred at room temperature for 18 hours. The reaction is quenched by the addition of saturated NaHCO3. The mixture is extracted with DCM (3x), the organic extracts are dried over Na2SO4, filtered, and concentrated to give the crude title compound as a mixture of regioisomers (130 mg, 100%) as a yellow oil. ES/MS (m/z): 309 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | Acetic acid (42 pL, 0.73 mmcl) was added to a solution of 1 -(tert-butyl) 2-methyl (2S,4R)-4-aminopyrrolidine- 1 ,2-dicarboxylate (7.48 g, 30.6 mmcl) and tert-butyl (2-oxoethyl)carbamate (4.64 g, 29.2 mmcl) in MeOH (194 mL) and the reaction stirred at roomtemperature for 3 h. The solution was cooled to 0 00 and sodium triacetoxyborohydride (9.27 g,43.7 mmol) was added portion-wise. The reaction stirred overnight while slowly warming toroom temperature. The reaction mixture was concentrated under reduced pressure and theresulting residue was diluted with DCM washed sequentially with saturated sodiumbicarbonate, water and saturated sodium chloride. The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The crude material was purified by silica gel chromatography (DCM/EtOAc/MeOH) to afford 1 -tert-butyl 2-methyl (2S,4R)-4-[2-(tert- butoxycarbonylamino)ethylamino]pyrrolidine- 1 ,2-dicarboxylate (Intermediate 72, 4.77 g, 42%yield) as a colorless oil. 1H NMR (500MHz, DMSO-d6) 51.25- 1.48 (20H, m), 1.84-2.07 (3H,m), 2.88-2.98 (2H, m), 3.02-3.17 (1H, m), 3.17-3.27 (1H, m), 3.40-3.51 (1H, m), 3.64(3H,s), 4.14-4.24 (1 H, m), 6.63-6.74 (1 H, m); m/z: (ESj [M+H] = 388. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | A solution of /ert-butyl (2-oxoethyl)carbamate (4.89 g, 30.7 mmol) in 1,2- dichloroethane (50 mL) was added to a solution of l-(tert-butyl) 3-methyl piperazine- 1,3- dicarboxylate (5 g, 20.5 mmol) in l,2-dichloroethane (25 mL). The solution stirred at 25 C under nitrogen atmosphere for 30 min. Sodium triacetoxyborohydride (8.69 g, 41.0 mmol) was added, and the resulting mixture stirred at 25 C for 15 h. The reaction was quenched by the addition of water (50 mL) at 25 C. The resulting mixture was extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, and the solids were filtered out. The filtrate was concentrated under vacuum. The residue was purified by silica gel chromatography (eluting with 1 : 1 ethyl acetate/petroleum ether) to afford l-ter/-butyl 3- methyl 4-(2-(/er/-butoxycarbonylamino)ethyl)piperazine-l,3-dicarboxylate as yellow oil (5.1 g, 64%). LCMS (ES, m/z): 388 [M+H]+. |