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CAS No. : | 543-24-8 | MDL No. : | MFCD00004275 |
Formula : | C4H7NO3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OKJIRPAQVSHGFK-UHFFFAOYSA-N |
M.W : | 117.10 | Pubchem ID : | 10972 |
Synonyms : |
Aceturic acid;Acetamidoacetic acid;NSC 7605;NAGly
|
Num. heavy atoms : | 8 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.5 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 2.0 |
Molar Refractivity : | 26.12 |
TPSA : | 66.4 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -7.85 cm/s |
Log Po/w (iLOGP) : | 0.67 |
Log Po/w (XLOGP3) : | -1.18 |
Log Po/w (WLOGP) : | -0.79 |
Log Po/w (MLOGP) : | -0.95 |
Log Po/w (SILICOS-IT) : | -0.8 |
Consensus Log Po/w : | -0.61 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | 0.38 |
Solubility : | 278.0 mg/ml ; 2.37 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 0.28 |
Solubility : | 223.0 mg/ml ; 1.9 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | 0.01 |
Solubility : | 119.0 mg/ml ; 1.02 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-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 |
---|---|---|
100% | With sodium acetate In acetic anhydride at 120℃; for 7 h; | General procedure: A mixture of aromatic aldehyde (100 mmol), N-acylglycine (10.7 g, 120 mmol), sodium acetate (51 g, 500 mmol) were mixed and heated at 120 °C for 7 h. After completion of the reaction, the resulting solution was kept in refrigerator overnight to obtain a solidified mass which was triturated with cold water and ethanol. The resulting yellow crystals were collect and dried to give 4-(arylmethylene)-2-methyl-5(4H)-oxazolone (2). |
74.25% | Heating | General procedure: A mixture of aldehyde (1 mol), acetyl glycine (1, 1 mol), acetic anhydride (3 mol) and anhydrous potassium acetate (1 mol) was heated on an electric hot plate with constant shaking till the mixture liquefied. Then the content of RBF was further heated on water bath for 2 h. To this, 100 mL of ethanol was added slowly and allowed the mixture to stand overnight. The crystalline product was separated by filtration, washed with 25 mL of ice-cold alcohol and then finally washed with 25 mL of boiling water and recrystallized using suitable solvent. |
70% | at 160℃; for 1 h; | N-Acetylglycine (0.80g,6.80mmol), benzaldehyde (1.08g, 10.20mmol) and sodium acetate(0.41g, 0.50mmol) were added to a round-bottomed flask. To this mixture wascarefully added acetic anhydride (1.73g, 1.6mL, 17.00mmol). The mixture washeated at 160°C under stirring for 1 h. The resulting solution was cooled atroom temperature and stored in fridge at 2-4°C for 24 h. The mixture was washedwith cold water, filtered, washed again with cold water and small amount of Et2O(x2)and dried to afford the desired product. |
38% | at 95 - 135℃; for 4 h; | General procedure: To a solution of N-acylglycine in acetic anhydride (reaction concentration=1 M) was added sodium acetate (0.63 equiv) and aryl-aldehyde (1.25 equiv) at room temperature. The reaction mixture was heated at 95-135 °C for the specific time (monitored by TLC). Ice was added to the reaction mixture and the resulting solution was cooled to 0 °C overnight. The precipitate was collected by filtration and the solid was recrylstallized to give the product. Alternatively, the aqueous solution was extracted by CHCl3 and the product was purified by flash column chromatography. |
32% | for 1 h; Reflux | 4-Benzylidene-2-methyloxazol-5(4H)-one synthesis: To a suspension of 25 acetylglycine (5.86 g, 50 mmol), 26 sodium acetate (4.10 g, 50 mmol), in 27 acetic anhydride (47.3 mL, 500 mmol), was added 28 benzaldehyde (5.11 mL, 50 mmol). The reaction mixture was heated in a 100 C oil bath for 10 min to dissolve. A reflux condenser was then added and the bath heated to 140 C for exactly 1 h. The reaction flask was then plunged into an ice-water bath with stirring and allowed to stir for 1 h. After 1 h, ice cold 29 water (47 mL) was added to the suspension of yellow solid in a dark red solution. The product was collected on a fritted glass funnel, washed with ice cold water (3×50 mL) with stirring in the funnel. The crude product was dried in a desiccators over solid 30 KOH overnight to provide 4.6 g of product as a yellow powder. This material was recrystallized from 85 mL of hot 2-propanol, cooling slowly to room temp, chilled in an ice bath, and then collected by filtration to provide 2.98 g, 32percent yield of purified 31 4-benzylidene-2-methyloxazol-5(4H)-one: mp 148-151 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With sodium acetate; acetic anhydride; for 1.0h;Reflux; | General procedure: (Z)-2-methyl-4-(4-methoxybenzylidene)-5(4H)oxazolone (1a) 1a-d. In a mixture of Nacetylglycine(1.17g, 10.0mmol), anisaldehyde (2.04g, 15mmol) and sodium acetate(0.60g, 7.35mmol) was slowly added acetic anhydride (2.55g, 25mmol). The resultingmixture was refluxed under vigorous stirring for 1h. The dark brown solution was cooledat room temperature, water was added and kept at 4C overnight to allow completeprecipitation. The solid was filtered and washed with water, ice-cold EtOH (×3) andEt2O:petroleum ether (1:1). The completion of the reaction and the purity of compoundwas determined, in principle, by TLC using blue stain and dinitrophenylhydrazine (DNPstain) to monitor the disappearance of the aldehyde. The product was dried under vacuumand P2O5 and used without further purification. For analytical purposes, it wasrecrystallized from EtOH to give light orange crystals. |
With sodium acetate; In acetic anhydride; at 100 - 110℃; | General procedure: Furthermore, the general procedure for the synthesis of azalactones 2(a-k) is the following:[6] to 1 with the adequate substituent R1 (1 equivalent, 20 mmol) and sodium acetate (1 equivalent, 20 mmol) in 18.4 ml of acetic anhydride was added the corresponding aldehyde with the required R2 group (1 equivalent, 20mmol). The resulting mixture was stirred for 4 hours at 100-110 oC. Then, the mixture was left stirring overnight at 25 oC. After this time, the target azalactone precipitated, and was separated by filtration and washed with 100 ml of cold Et2O. The resulting solid was purified by flash chromatography on silica gel (2:1hexanes/EtOAc) to obtain the Z isomerof (2a-v) in 60-90% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With toluene-4-sulfonic acid; at 90℃; | To a solution of N-acetylglycine (3 g) in EtOH (40 ml) under Ar was added p-toluenesulfonic acid (441 mg). The mixture was heated at 90C overnight. The cooled mixture was concentrated under vacuum and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The organic phase was concentrated under vacuum to give 2.5 g (69%) of the title compound. 1H-NMR (delta, ppm, CDCl3): 6.00 (bs, 1 H), 4.23 (q, 2H), 4.03 (d, 2H), 2.05 (s, 3H), 1.30 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | In acetic anhydride for 3h; Heating; Na-acetate; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium acetate; In acetic anhydride; for 16h;Heating / reflux; | A. 4-(5-Chloro-thiophen-2-ylmethylene)-2-methyl-4H-oxazol-5-one. A mixture consisting of 5-chlorothiophene-2-carboxaldehyde (1.00 g, 6.82 mmol), N-acetylglycine (0.96 g, 8.18 mmol), NaOAc (0.67 g, 8.18 mmol) in Ac2O (5 ML) is warmed at reflux for 16 hours.The reaction mixture is cooled to ambient temperature and diluted with dilute aqueous NaOH (0.5 M, 100 ML) and CH2Cl2 (100 ML).The layers are separated and the organic phase is washed with aqueous NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated to provide 1.5 g (100percent) of the title compound as a colorless oil which is used without further purification in the next reaction. 1H NMR (300 MHz, CDCl3) delta2.39 (s, 3H), 6.94 (d, J=4.0 Hz, 1H), 7.21 (s, 1H), 7.26 (d, J=4.0 Hz, 1H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
~ 80% | With sodium acetate; acetic anhydride; In DMF (N,N-dimethyl-formamide); at 50 - 100℃; for 4.5h; | The second step was the Erlenmeyer condensation of 5-bromo-2-hydroxy-3- nitrobenzaldehyde (2*) with N-acetyl-glycine to yield N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-yl) acetamide (3*). 0 O IrOH H Bu H H 0 Br Ny CH3 zizi OH Ac20 I O-'O NO2 NaOAc NO2 (2*) DMF (3*) step 2 To a mixture of 1.0 mol of <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*), 1.0 mol of N-acetylglycine and 1.0 mol of anhydrous sodium acetate, 800 ml of N-methyl-2- pyrrolidone are added. The mixture was stirred and heated to 50 C. Then 2. 2 mol of acetic anhydride was run into the reaction vessel in approximately 30 minutes. The reaction mixture was heated to 100C. During heating the reacting mixture became homogeneous for a while ; shortly afterwards a solid was formed, making stirring troublesome. After heating at 100C for 4 hours, the mixture was cooled to 80C and 1, 100 ml of acetic acid (98%) was added. Thereafter stirring of the mixture was easy. Next, the mixture was cooled to room temperature, and stirred for 60 minutes. The precipitate was collected on a filter and washed twice with 625 mi acetic acid (80%), five times with 900 mi water, and once with 300 mi acetone. The product was dried in an air stream at 40C for 24 hours, and had a purity of 98% as shown by NMR analysis. <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*) had a characteristic shift of 8 10.4 ppm; the characteristic chemical shift of N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-yl) acetamide (3*) was 8 8.72 ppm The overall yield of this step was approximately 80% (crude on crude). |
~ 80% | With sodium acetate; acetic anhydride; In DMF (N,N-dimethyl-formamide); at 50 - 100℃; for 4.5h; | The second step was the Erlenmeyer condensation of 5-bromo-2-hydroxy-3- nitrobenzaldehyde (2*) with N-acetyl-glycine to yield N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-yl) acetamide (3*). ? N-yOH H Br H 0 Br N CH3 OH I OH Ac20 I O O NO2 NaOAc NO2 (2*) DMF (3) step 2 To a mixture of 1.0 mol of <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*), 1.0 mol of N-acetylglycine and 1.0 mol of anhydrous sodium acetate, 800 ml of N-methyl-2- pyrrolidone are added. The mixture was stirred and heated to 50 C. Then 2.2 mol of acetic anhydride was run into the reaction vessel in approximately 30 minutes. The reaction mixture was heated to 100C. During heating the reacting mixture became homogeneous for a while ; shortly afterwards a solid was formed, making stirring troublesome. After heating at 100C for 4 hours, the mixture was cooled to 80C and 1, 100 ml of acetic acid (98%) was added. Thereafter stirring of the mixture was easy. Next, the mixture was cooled to room temperature, and stirred for 60 minutes. The precipitate was collected on a filter and washed twice with 625 mi acetic acid (80%), five times with 900 ml water, and once with 300 ml acetone. The product was dried in an air stream at 40C for 24 hours, and had a purity of 98% as shown by NMR analysis. <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*) had a characteristic shift of 8 10.4 ppm; the characteristic chemical shift of N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-ylacetamide (3*) was 8 8.72 ppm The overall yield of this step was approximately 80% (crude on crude). |
~ 80% | With sodium acetate; acetic anhydride; In 1-methyl-pyrrolidin-2-one; at 50 - 100℃; for 4.5h; | The second step was the Erienmeyer condensation of 5-bromo-2-hydroxy-3- nitrobenzaldehyde (2*) with N-acetyl-glycine to yield N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-yl) acetamide (3*). o Nir" o 0, rOH H Br H H p Br NCH3 OH Ac20 I O O NO7 NaOAc NO2 (2*) DMF (3*) step 2 To a mixture of 1.0 mol of <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*), 1. 0 mol of N-acetylglycine and 1.0 mol of anhydrous sodium acetate, 800 ml of N-methyl-2- pyrrolidone are added. The mixture was stirred and heated to 50C. Then 2.2 mol of acetic anhydride was run into the reaction vessel in approximately 30 minutes. The reaction mixture was heated to 100C. During heating the reacting mixture became homogeneous for a while ; shortly afterwards a solid was formed, making stirring troublesome. After heating at 100C for 4 hours, the mixture was cooled to 80C and 1, 100 ml of acetic acid (98%) was added. Thereafter stirring of the mixture was easy. Next, the mixture was cooled to room temperature, and stirred for 60 minutes. The precipitate was collected on a filter and washed twice with 625 ml acetic acid (80%), five times with 900 ml water, and once with 300 mi acetone. The product was dried in an air stream at 40C for 24 hours, and had a purity of 98% as shown by NMR analysis. <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*) had a characteristic shift of 8 10. 4 ppm; the characteristic chemical shift of N- (6-bromo-8-nitro-2-oxo-2H-1- benzopyran-3-yi) acetamide (3*) was 8 8.72 ppm The overall yield of this step was approximately 80% (crude on crude). |
80% | With sodium acetate; acetic anhydride; In 1-methyl-pyrrolidin-2-one; at 50 - 100℃; for 4.5h; | To a mixture of 1.0 mol of <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*), 1.0 mol of N-acetylglycine and 1.0 mol of anhydrous sodium acetate, 800 ml of N-methyl-2-pyrrolidone are added. The mixture was stirred and heated to 50 C. Then 2.2 mol of acetic anhydride was run into the reaction vessel in approximately 30 minutes. The reaction mixture was heated to 100 C. During heating the reacting mixture became homogeneous for a while; shortly afterwards a solid was formed, making stirring troublesome. After heating at 100 C. for 4 hours, the mixture was cooled to 80 C. and 1,100 ml of acetic acid (98%) was added. Thereafter stirring of the mixture was easy. Next, the mixture was cooled to room temperature, and stirred for 60 minutes. The precipitate was collected on a filter and washed twice with 625 ml acetic acid (80%), five times with 900 ml water, and once with 300 ml acetone. The product was dried in an air stream at 40 C. for 24 hours, and had a purity of 98% as shown by NMR analysis. <strong>[16634-88-1]5-bromo-2-hydroxy-3-nitrobenzaldehyde</strong> (2*) had a characteristic shift of delta 10.4 ppm; the characteristic chemical shift of N-(6-bromo-8-nitro-2-oxo-2H-1-benzopyran-3-yl)acetamide (3*) was delta 8.72 ppm. The overall yield of this step was approximately 80% (crude on crude). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | 1a (Z,E)-2-acetylamino-3-(3,4-dibromo-phenyl)-acrylic acid A mixture of 22.08 g (83.66 mmol) of <strong>[74003-55-7]3,4-dibromobenzaldehyde</strong>, 14.7 g (125.5 mmol) N-acetylglycine and 10.29 g (125.5 mmol) NaOAc in 100 mL acetic anhydride were heated to 118 C. (internal temperature) for 1.5 h. After the reaction had ended the reaction mixture was cooled to approx. 100 C. and then combined batchwise with 20 g ice (exothermic reaction), while the internal temperature was kept below 120 C. The reaction mixture was heated to 95 C. for a further 2 h, then added to a mixture of 240 mL water and 120 mL toluene and stirred for 1 h at RT. The precipitate was suction filtered, washed with 50 mL each of toluene and water and dried overnight at 40 C. in the circulating air dryer. Yield: 20.82 g (69% of theory) ESI-MS: (M+H+>=362/364/366 (2 Br) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate In dichloromethane; water; acetic anhydride; acetonitrile | VIII.1 EXAMPLE VIII-1 STR37 EXAMPLE VIII-1 STR37 To a suspension of 179 g (0.827 mol) of 3-(4-chlorophenyl)-benzaldehyde in 1 l of acetic anhydride there are added 117.1 g (1 mol) of N-acetylglycine and 82 g (1 mol) of sodium acetate, and the mixture is stirred for 18 hours at 130° C. For working up, the solvent is distilled off under a water pump vacuum, the residue is taken up in 2 l of dichloromethane, the mixture is washed three times using 1 l of water each time, dried over sodium sulphate and concentrated in vacuo. The residue is crystallized by stirring with 300 ml of acetonitrile, filtered off with suction and dried. 115.9 g (47% of theory) of 4-[3-(4-chlorophenyl)-benzylidene]-2-methyl-1,3-oxazolin-5-one of melting point 150° C. are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 13 6-(4-acetylglycylaminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone A mixed acid anhydride was prepared from 0.58 g of acetylglycin under the almost same conditions as described in Example 11 and then reacted with 6-(p-aminophenyl)-5-methyl-4,5-dihydropyridazinone to obtain the end product. Recrystallization from dimethylformamide and water afforded 410 mg of the end product. M.P. 260 C. or higher. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
TV-Acetylglycine (0.031 ml, 0.22 mmol) was dissolved in 1 : 1 1 ON NaOH/THF (2 ml) and was stirred at 50 C for 1 h. The mixture was neutralized to pH 4 with 6N HCl, then concentrated. The yellowish solid was diluted with 1:1 MeOHZCH2Cl2 (25 ml), filtered to remove inorganic salts, and concentrated. The solid obtained was diluted again with 1:1 MeOH/CH2Cl2 and concentrated to give (2-oxo-pyrrolidin-l-yl)-acetic acid as a white solid. The crude product was used in the next reaction without purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With sodium acetate; acetic anhydride In ethyl acetate Reflux; | |
Stage #1: acetic anhydride; 4-(hydroxylmethyl)benzaldehyde With sodium acetate In ethyl acetate at 104 - 106℃; for 0.25h; Heating / reflux; Stage #2: N-acetylglycine In ethyl acetate at 93 - 95℃; for 18h; Heating / reflux; | 2 To a 2 L three neck flask, fitted with an overhead agitator, thermometer and condenser sodium acetate (59.2 g), (4-hydroxymethyl)benzaldehyde (2) (69.0 g), ethyl acetate (100 ml) and acetic anhydride (120ml) were charged. The slurry was heated to reflux (104-106 °C) and maintained at reflux for 15 minutes before cooling to below 40 0C. iV-acetylglycine (42.2 g) and ethyl acetate (100 ml) were charged, the resultant mixture was heated to reflux (93-95 °C) and maintained for 18 hours. The batch was cooled to below 60 0C at which point it solidified and water (400ml) was added, the resultant solid was isolated by vacuum filtration, the slurry washed in water (300 ml), then washed in MTBE (300 ml) and then displacement washed with MTBE (100 ml). The yellow solids were dried under vacuum at 45 0C to give 56.2 g of (3); purity by GC was 96.1%; 1H NMR (400 MHz, CDCl3) δ ppm 8.08 (2H, d, J= 7.8 Hz), 7.42 (2H, d, J= 7.8 Hz), 7.13 (IH, s), 5.14 (2H, s), 2.41 (3H, s) and 2.13 (3H, s); 13C NMR (100 MHz, CDCl3) 6 ppm 171.2, 168.1, 166.7, 139.4, 133.4, 133.2, 132.7, 131.1, 128.7, 66.1, 21.4 and 16.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate; acetic anhydride; at 140℃; for 8h; | 1.38g of 2,4-dihydroxybenzaldehyde, 1.17g of acetylglycine, 2.48g of sodium acetate dissolved in 25ml of acetic anhydride, heated to 140 condensed reflux reaction 8 hours, adding a small amount of distilled water, filtered and filtered to obtain solid . The solid was dissolved in a mixed solution of concentrated hydrochloric acid and ethanol at a volume ratio of 2: 1. The reaction was condensed at 80 C for 3 hours. After cooling, the solution was adjusted to pH 6.5 with 30% sodium hydroxide solution and the solid was collected by suction filtration. The solid was dried in a vacuum desiccator and recrystallized from ethanol to give the product 3-amino-7-hydroxycoumarin. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: N-acetylglycine With triethylamine; isobutyl chloroformate In dichloromethane at -10℃; for 0.333333h; Stage #2: 2-amino-4'-fluorobenzophenone In dichloromethane at 20℃; | 70 Intermediate 70: IV2-acetyl-M-[2-(4-fluorobenzoyl)phenvl]gL Icinandde; A solution of N-acetylglycine (2.96 g, 0.025 mol) in dry DCM was cooled to 0°C was and treated with triethylamine (3.52 ml, 0.025 mol) followed by isobutyl chloroformate (3.27 m1L, 0.025 mol). The resulting mixture was stirred at-10°C for 20 minutes and treated dropwise with a solution of (2-aminophenyl) (4-fluorophenyl) methanone (5 g, 0.023 mol) in DCM (20 ml) and then stirred at room temperature overnight. The mixture was extracted with DCM and washed successively with 0.1 M sodium hydroxide and water. The organic layer was dried over MgS04 and concentrated under reduced pressure to give the N2-acetyl-N¹-[2-( 4- fluorobenzoyl) phenyl]glycinamide (7.23 g, 0.021 mol, 91 %) as a solid. LCMS (ESI+) 337 [M+Na]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium acetate; acetic anhydride; at 120℃; for 4h; | Compound 2 and the same amount of acetylglycine, sodium acetate Dissolved in acetic anhydride, heated at 120 C reflux 4h, cooled to 0 C precipitation of crystals, To give compound 3. |
74% | With sodium acetate; acetic anhydride; at 120℃; for 4h; | A mixture of aldehyde 5 (2.94 g, 10 mmol), NaOAc (0.82 g, 10 mmol), and N-acetylglycine (1.17 g, 10 mmol) in Ac2O (20 mL) was stirred at 120 C for 4 h. The reaction mixture was cooled to room temperature and the yellow solid which precipitated was filtered and washed with cold 1:1 pentane/Et2O to yield 6 as a yellow solid (2.78 g, 74%); mp: 154-155 C; IR (neat) (numax/cm-1) 3233, 2927, 1692, 1662, 1633, 1468, 1416, 1365, 1255, 1201, 981, 902, 721. 1H NMR (500 MHz, DMSO-d6): delta 2.40 (s, 3H), 3.84 (s, 3H), 7.16 (s, 1H), 8.47 (s, 2H). 13C NMR (125.7 MHz, DMSO-d6): delta 15.52, 60.73, 117.90, 125.70, 132.28, 133.88, 135.66, 154.95, 166.88, 168.04. Anal. Calcd for C12H9Br2NO3: C, 38.43; H, 2.42; N, 3.73. Found: C, 38.40; H, 2.46; N, 3.70. |
With sodium acetate; acetic anhydride; at 80℃; for 3h; | General procedure: General Procedure for the Formation of AzlactonesAldehyde 19a-d, acetylglycine (1.5 equiv.) and anhyd. NaOAc (1.5 equiv.) were dissolved inAc2O (10-15 mL) and the reaction mixture was stirred at 80 C overnight. Afterwards, the reactionmixture was cooled to room temperature and poured into water (50 mL). The formed precipitate filtered, washed with water (4 × 20 mL) and dried in vacuo. The obtained crude product 20a-d wasused in the subsequent step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h; | A mixture of 4 (0.69 g, 2 mmol), N-acetylglycine (0.234 g, 2 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI, 0.383 g, 2 mmol) and catalytic amount of 1-hydroxybenzotriazole (HOBt) in anhydrous dichloromethane (10 mL) was stirred at room temperature for 12 h. Then the reaction solution was quenched with water, the separated organic phase was washed with 5 % citric acid aqueous solution followed by 10 % ammonium chloride aqueous solution. Then the organic phase was dried over anhydrous MgSO4 and concentrated under vacuum. The product was yielded as colourless oil, which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) delta: 1.37-1.72 (m, 24H, 2 × Boc, NCH2(CH2)2CH2NH, NCH2CH2CH2NH), 1.98 (s, 3H, NHCOCH3), 3.00-3.37 (m, 8H, 2 × NCH2, 2 × NHCH2), 3.96-3.99 (m, 2H, COCH2NH), 4.64 (s, 1H, BocNH), 5.16 (s, 1H, BocNH), 6.57 (s, 1H, NHCOCH3) ppm. 13C NMR (CDCl3, 400 MHz) delta: 23.01 (NHCOCH3), 24.71, 25.73, 27.56, 28.37, 28.40, 28.42, 28.44, 41.18, 41.23, 42.94, 44.39, 45.62, 46.46, 79.13 (OC(CH3)3), 79.34 (OC(CH3)3), 156.04 (NHCOOtBu), 167.71 (NHCOCH2NH), 168.20 (NHCOCH2NH), 170.09 (NHCOCH3) ppm. ESI-MS m/z 445.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetic anhydride; at 90℃; for 9h; | A mixture of 43.6 g of 3-dimethylamino-l- (pyridin-3- yl ) -propenone, 28.9 g of N-acetylglycine and 300 ml of acetic anhydride was stirred with heating at 90C for 9 hours. After cooling down to room temperature, 200 ml of ethanol was added, and the deposited precipitate was filtrated. The filtrated product was washed with 100 ml of ethanol, and dried under reduced pressure to obtain 25.0 g of N- [2-OXO-6- (pyridin-3-yl) -2H-pyran-3-yl] - acetamide (hereinafter, referred to as the inventive com ound 1 ) .Inventive compound 11 H-NMR (DMSO-D6) delta: 9.80 (1H, s), 9.03-9.00 (1H, m) ,8.64-8.61 (1H, m) , 8.26 (1H, d) , 8.18-8.15 (1H, m) ,7.55-7.51 (1H, m) , 7.24 (1H, d) , 2.15 (3H, s).1 H-NMR (CDCI3) delta: 9.02-9.00 (1H, m) , 8.66-8.63 (1H, m) , 8.39 (1H, d) , 8.08-8.04 (1H, m) , 8.04 (1H, s), 7.39 (1H, dd) , 6.80 (1H, d) , 2.25 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sodium acetate; acetic anhydride Reflux; | 1 Preparation (E)-2-methyl-4-((5-pheny]furan-2-yl)methylene)oxazol-5(4H)-one 47 (JL120)[0217] To a mixture of 5-phenyl-2-furaldehyde 4 (517 mg, 3.0 mmol), N-acetylglycine 46 (457 mg, 3.9 mmol) and sodium acetate (1230 mg, 15.0 mmol) was added acetic anhydride (30 mL). The reaction mixture was refluxed overnight, then the excess solvent was removed in vacuo. The residue was diluted with ethyl acetate (200 mL), then washed with water (2 X 50 mL). The organic layer was dried with brine and MgS04, then concentrated in vacuo. Flash column chromatography on silica gel (n-hexanes : ethyl acetate = 10: 1) of the residue afforded the desired product 47 (JL120) in 53% yield (400 mg, orange solid). XH NMR (400 MHz, CDC13): 7.77 (d, J= 7.2 Hz, 2H), 7.52 (d, J= 3.6 Hz, 1H), 7.44 (t, J= 7.2 Hz, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.12 (s, 1H), 6.89 (d, J= 3.6 Hz, 1H), 2.41 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
5.95 g | [0035] Ac-Gly-OH a (3.77 g, 32.2 mmol) and triethylamine (6.7 mL, 48.1 mmol) were dissolved in 160 mL THF and cooled to -10?, and isobutylchloroformate (5.02 g, 38.6 mmol) was added. The mixture was stirred at -10? for 1 hr. H-beta-Ala-OBzl.PTSA e (11.26 g, 32.0 mmol) and triethylamine (6.7 mL, 48.1 mmol) was dissolved in 160 mL THF, and added into mix anhydride solution. The reaction mixture was stirred at room temperature overnight. The salt was filtrated off and THF was removed in vacuum. The residue obtained was purified by column chromatography using ethyl acetate and heptane as eluent to obtain 5.95 g Ac-Gly-beta-Ala-OBzl f. | |
69 g | With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 2h;Ionic liquid; | First, 3-amino-propionic acid benzyl ester. P-toluenesulfonate (125g) and acetyl glycine (44g) were mixed in triethylamine (90g) to form an ionic liquid mixture,Then, a dichloromethane solution (1000 g) containing N, N'-dicyclohexylcarbodiimide (88 g) and 1-hydroxy-benzotriazole (2.4 g) was added and the reaction was carried out at room temperature for at least 2 hours, And the reaction was carried out using a high-pressure liquid chromatograph. After the completion of the reaction, the insoluble solid was removed by filtration and subjected to extraction and washing to remove the organic salts of triethylamine. The dichloromethane was concentrated and the resulting residue was removed, Mixed with water and dispersed to give an off-white solid which was then crystallized from acetone to give a white solid (69 g). See Figure 2,Proton nuclear magnetic resonance spectroscopy demonstrated the above white solid is 3 (2-acetamido - acetamido) - propionic acid benzyl ester, using high pressure liquid chromatography analysis, greater than 99% purity. |
5.95 g | Acetylglycine (a; Ac-Gly-OH; 3.77 g, 32.2 mmol) and triethylamine (6.7 mL; 48.1 mmol) were dissolved in 160 ml of tetrahydrofuran (THF)After cooling to -10 C,Was added isobutyl chloroformate (isobutylchloroformate; 5.02g, 38.6 mmol).The mixed solution was stirred at -10 C for 1 hour. In addition, beta-phenylalanilate p-toluenesulfonate is added(e; H-beta-Ala-OBzl. PTSA; 11.26 g, 32.0 mmol)And triethylamine (6.7 ml; 48.1 mmol) were dissolved in 160 ml of tetrahydrofuran (THF)This was added to the above mixed acid anhydride solution.The reaction mixture was stirred at room temperature overnight.The salt is filtered,The THF was removed by vacuum drying.The residue was purified by column chromatography,Using ethyl acetate and heptane as eluent,About 5.95 g of intermediate f (Ac-Gly-beta-Ala-OBzl) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With zinc(II) oxide In ethanol at 25℃; for 0.25h; | Synthesis of the 4-(arylmethylidene)-2-phenyl/methyl-5-(4H)-oxazolones derivatives(2-7) General procedure: A mixture of the required aldehyde (1 mmol), N-benzoylglycine/N-acetylglycine (1 mmol),acetic anhydride (3 mmol), ZnO as a catalyst (0.05 mmol) and 15 mL ethanol was stirred atroom temperature, 25 °C (Scheme 1). After a certain period, the syrupy reaction mixture was solidified and the reaction was completed (Table I). After the final product had been obtained,20 mL more of cold ethanol was added. The solid was filtered off, dried and washed with hotwater before recrystallization of the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With zinc(II) oxide; In ethanol; at 25℃; for 0.25h; | General procedure: A mixture of the required aldehyde (1 mmol), N-benzoylglycine/N-acetylglycine (1 mmol),acetic anhydride (3 mmol), ZnO as a catalyst (0.05 mmol) and 15 mL ethanol was stirred atroom temperature, 25 C (Scheme 1). After a certain period, the syrupy reaction mixture was solidified and the reaction was completed (Table I). After the final product had been obtained,20 mL more of cold ethanol was added. The solid was filtered off, dried and washed with hotwater before recrystallization of the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With zinc(II) oxide; In ethanol; at 25℃; for 0.166667h; | General procedure: A mixture of the required aldehyde (1 mmol), N-benzoylglycine/N-acetylglycine (1 mmol),acetic anhydride (3 mmol), ZnO as a catalyst (0.05 mmol) and 15 mL ethanol was stirred atroom temperature, 25 C (Scheme 1). After a certain period, the syrupy reaction mixture was solidified and the reaction was completed (Table I). After the final product had been obtained,20 mL more of cold ethanol was added. The solid was filtered off, dried and washed with hotwater before recrystallization of the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With sodium acetate In acetic anhydride for 4h; Inert atmosphere; Reflux; | 4.3. General procedure-2: synthesis of the oxazoles 2, or acrylic acids, 3 General procedure: 5 mmol of the substituted benzaldehyde was dissolved in 20 mL of acetic anhydride then 1.2 equiv. of N-acetyl glycine and 5 equiv. of sodium acetate were added and the reaction was stirred under reflux for 4 h. Then solvent was partially evaporated then was poured into 50 mL of crushed ice and stirred vigorously for 30 min. A precipitate was obtained which was separated and washed with cold water and dried under vacuum to get the oxazolyl product 2, or its hydrolyzed acrylic acid, 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium acetate; sodium carbonate; In acetic anhydride; | Synthesis of (Z)-4-(3-fluoro-4-hydroxybenzylidene)-2-methyloxazole-5(4H)-one Commercially available <strong>[405-05-0]3-fluoro-4-hydroxybenzaldehyde</strong> (14 g, 0.1 mol), N-acetylglycine (14 g, 0.12 mol), sodium carbonate (10.6 g, 0.1 mol) and sodium acetate (16.6 g, 0.2 mol) were mixed at r.t. in 60 mL of acetic anhydride and stirred at moderate heating until full dissolution of carbonate. Then the mixture was refluxed for 2 hours, cooled down to r.t. and diluted with water (200 mL). The precipitate was filtered and used without further purification: 22.34 g. (Yield -85percent) 1H NMR (CDCl3) delta 7.51 (m, 2H), 7.43 (d, J=11.0 Hz, 1H), 6.90 (t, J=7.3 Hz, 1H), 6.55 (m, 1H), 2.24 (s, 3H). |
85% | With sodium acetate; acetic anhydride; sodium carbonate; for 2h;Reflux; | Commercially available <strong>[405-05-0]3-fluoro-4-hydroxybenzaldehyde</strong> (14 g, 0.1 mol), N-acetylglycine (14 g, 0.12 mol), sodium carbonate (10.6 g, 0.1 mol) and sodium acetate (16.6 g, 0.2 mol) were mixed at r.t. in 60 mL of acetic anhydride and stirred at moderate heating until full dissolution of carbonate. Then the mixture was refluxed for 2 hours, cooled down to r.t. and diluted with water (200 mL). The precipitate was filtered and used without further purification: 22.34 g. (Yield ?85percent) 1H NMR (CDCl3) delta 7.51 (m, 2H), 7.43 (d, J=11.0 Hz, 1H), 6.90 (t, J=7.3 Hz, 1H), 6.55 (m, 1H), 2.24 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: N-acetylglycine With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 120℃; for 0.0833333h; Microwave irradiation; Stage #2: 6-methoxysalicylaldehyde With triethylsilane In N,N-dimethyl-formamide at 200℃; for 0.2h; Microwave irradiation; | General procedure for coumarins 6 and 7. General procedure: Corresponding acid (2 eq) and CDI (2.1 eq) were dissolved in the minimum amount of anhydrous DMF and microwaved at 120 °C for 5 minutes. 2-Hydroxy-6-methoxybenzaldehyde (1 eq) and TEA (1 eq) were added and the reaction was heated at 200 °C during the required time. The solvent was removed under vacuum, ethyl acetate was added and the mixture was washed with NaHCO3 and brine. The organic layer was dried over MgSO4, filtered, and evaporated under reduced pressure. The crude was purified by chromatographed (DCM to DCM/ethyl acetate) to afford the corresponding coumarin. |
With sodium acetate; acetic anhydride for 6h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | at 25℃; for 1.5h; | (1) A mixture of (30.0 g, 270.3mmol) and acetic anhydride (150.0mL) was stirred at room temperature for 1.5h.After completion of the reaction, the white precipitate was filtered and washed with water. Then, the white precipitatewas dried under vaccum to afford III (30.0 g, 95%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: 4.1.4. General procedure C: condensation of amidoxime and amino acid A solution of amino acid (1.5 equiv), HATU (1.5 equiv) and DIEA(1.5 equiv) in anhydrous DMF was stirred at room temperature for15-60 min. Amidoxime (1.0 equiv) was then added, and the result-ing mixture was further stirred at room temperature for 25-120 min and then at 80-100 C for 0.5-9 h. After the reaction,the mixture was diluted with AcOEt and washed with aq NaHCO3.The organic layer was dried over Na2SO4, and the solvent wasremoved under reduced pressure. The residue was puried by sil-ica gel column chromatography to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: 4.1.6. General procedure E: removal of SEM group To a solution of SEM-protected compound (1.0 equiv) in THFwas added TBAF (3.0 equiv, 1 M in THF). The mixture was reuxedfor 11-20 h, then cooled to room temperature, and concentratedunder reduced pressure. The residue was puried by silica gel col-umn chromatography or PTLC to afford the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium acetate; acetic anhydride for 0.5h; Heating; | Synthesis of 4-((2-methoxyquinolin-3-yl)methylene)-2-methyloxazol-5(4H)-one (5) A mixture of 2-methoxyquinoline-3-carbaldehyde (1a) (0.125 mol), N-acetylglycine (0.125 mol), acetic anhydride (0.75 mol) and anhydrous sodium acetate (0.125 mol) was warmed in a water-bath till it became homogeneous solution (30 minutes). The formed precipitate was collected by filtration, washed with hot water and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In methanol at 25℃; for 48h; | Synthesis of peptidomimetics 1a-l by three-component Ugi reaction (General method). General procedure: The carboxylic acid (4.27 mmol) and the isocyanide (4.27 mmol) were added to a stirred solution of compound 2 (0.560 g, 4.27 mmol) in methanol (10 ml). The reaction mixture was stirred at room temperature for 2 days and concentrated in vacuo. A crude oil was obtained. After purification by silica gel column chromatography (eluent varied from n-hexane-EtOAc, 7:3, to pure EtOAc), the desired product was obtained as oil or foamy solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a mixture containing CTC Resin (0.2 mmol, 0.17 g, 1.2 mmol/g) and Fmoc-Met-OH (74.3 mg, 0.2 mmol, 1.0 eq) was added DCM (2.00 mL), then DIEA (6.00 eq) was added and mixed for 2 hours. And then MeOH (0.2 mL) was added and mixed for 30 min for capping. 20% piperidine in DMF was used for deblocking. And the others amino acids were coupled with 3 eq using activator reagents, HATU (2.85 eq) and DIPEA (6.0 eq) in DMF (2 mL). The reaction was monitored by ninhydrin color reaction or Tetrachloro-p-benzoquinone test. After synthesis completion, the peptide resin was washed with DMF X 3, MeOH X 3, and then dried under N2 bubbling overnight. After that the peptide resin was treated with 2.5%EDT/2.5%H20/95%TFA for 3 h for 2 times. The peptide solution was precipitated with cold tert-butyl methyl ether (8 mL) and centrifuged (2 min at 3000 rpm). The supernatant was decanted and the precipitate was washed twice with tert-butyl methyl ether (100 imL). The crude peptide was collected and dried under vacuum for 2 hours, then purified by prep-HPLC (General procedure, method 4) and then lyophilized to give the final product SEQ ID NO: 3 (175 mg, 3.1% yield). ESI-MS (M+1): 1993.9 calc. for C95H132N24O20S2: 1992.9, m/z found 997.5 [M/2+H]+ 665.4 [M/3+H]+. HPLC analytical method 4, Rt = 9.78 min. Following the same protocol as the one provided above for SEQ ID NO: 3, the remaining lineal peptides of this section were analogously prepared. In those cases wherein the C(t) of the peptide was amidated (being one of F or F - C(=0)NH2) a Rink Amide MBHA resin (Novabiochem, Cat N 431041-83-79) was used to perform the solid phase synthesis instead of the CTC Resin; and when the N(t) of the peptide was acetylated, an acetylated Gly residue (CH3-C(=0)-NH-CH2-C(=0)OH) was incorporated as the last amino acid in the solid phase synthesis). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; | 4-(2- methoxyphenyl)piperidine (50 mg, 0.26 mmol), acetylglycine (46 mg, 0.39 mmol, 1.5 equiv.) and N,N- diisopropylethylamine (DIPEA, 0.137 mL, 0.58 mmol, 3.0 equiv.) in anhydrous DMF (1.0 inL) were added EDC (75 mg, 0.39 mmol, 1.5 equiv.) and HO At (53 mg, 0.39 mmol, 1.5 equiv.). The reaction mixture was stirred at room temperature for -12 h before removing the solvent under reduced pressure. The remaining residue was purified by PTLC (CH2Cl2/MeOH, 9/1) providing the title compound 51 as a colorless oil (40 mg, 53%). l NMR (600 MHz, CDC13) delta 7.21 (ddd, J= 8.2, 7.4, 1.7 Hz, 1H), 7.10 (dd, J= 7.6, 1.8 Hz, 1H), 6.93 (td, J= 7.5, 1.1 Hz, 1H), 6.87 (dd, J= 8.2, 1.1 Hz, 1H), 6.67 (brs, 1H), 4.77 - 4.71 (m, 1H), 4.16 - 4.09 (m, 1H), 4.05 (dd, J= 17.3, 3.8 Hz, 1H), 3.83-3.81 (m, 4H), 3.24 - 3.12 (m, 2H), 2.75 (td, J= 12.9, 2.8 Hz, 1H), 2.05 (s, 3H), 1.94 - 1.85 (m, 2H), 1.68 - 1.52 (m, 2H). 13C NMR (151 MHz, CDC13) delta 23.07, 31.26, 32.12, 35.43, 41.40, 43.13, 45.30, 55.28, 110.42, 120.70, 126.38, 127.40, 132.74, 156.66, 166.03, 170.09. HRMS (ESI-TOF) calcd for Ci6H23N203 291.1703 (M+H+), found 291.1704. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | With sodium acetate; acetic anhydride; at 110℃; for 7h; | mixture of 6 (1.0 g, 5.45 mmol), N-acetylglycine (0.64 g, 5.45 mmol), anhydrous sodium acetate (1.8 g, 21.9 mmol), and acetic anhydride (2.6 mL, 27.55 mmol) was heated at 110 C for 7 h. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified by column chromatography to yield 7 (0.5 g, 35%) as white solid. 1H-NMR (CDCl3, 300 MHz), delta: 8.62 (s, 1H), 8.01 (br s, 1H), 6.89 (s, 1H), 6.83 (s, 1H), 3.94 (s, 3H), 3.92 (s, 3H), 2.24 (s, 3H); 13C-NMR (CDCl3, 75 MHz), delta: 169.2, 159.0, 151.2, 147.0, 145.3, 123.9, 122.1, 112.2, 108.0, 99.7, 56.3(2C), 24.7; FT-IR, numax (cm1): 3347, 1715, 1682, 1530, 1386, 1244, 1010;MS (EI), m/z (relative intensity): 263 (M+, 47), 221 (100), 206 (39), 178 (17), 150 (16), 122 (26); HRMS (ESI-pos), m/z calcd. for C13H13NO5Na [M + Na]+: 286.0686, measured: 286.0690. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate; acetic anhydride; at 80℃; for 3h; | General procedure: General Procedure for the Formation of AzlactonesAldehyde 19a-d, acetylglycine (1.5 equiv.) and anhyd. NaOAc (1.5 equiv.) were dissolved inAc2O (10-15 mL) and the reaction mixture was stirred at 80 C overnight. Afterwards, the reactionmixture was cooled to room temperature and poured into water (50 mL). The formed precipitate filtered, washed with water (4 × 20 mL) and dried in vacuo. The obtained crude product 20a-d wasused in the subsequent step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.7% | Stage #1: salicylaldehyde; N-acetylglycine With sodium acetate; acetic anhydride for 8h; Reflux; Stage #2: With sulfuric acid at 120℃; for 3h; | 33 Add salicylaldehyde (2.44g, 20mmol), acetylglycine (2.81g, 24mmol), anhydrous sodium acetate (4.92g, 60mmol), acetic anhydride (25mL) into a 250mL single-neck flask, and reflux for 8h. After the reaction is complete, After cooling, it was poured into 200 mL of ice water and stirred continuously to precipitate a solid, filtered and dried to obtain a yellow amide solid (1.10 g) with a yield of 27.1%.Add the above-mentioned yellow amide solid (1.02g, 5mmol), 70% concentrated sulfuric acid (7.5mL), reflux reaction at 120 for 3h in a 50mL single-necked flask. After the reaction is over, add 35mL ice water and 2N NaOH to adjust the pH to 6-7 and precipitate The solid was filtered, washed with water, dissolved by adding 50mL of dichloromethane, washed with 10mL×4 water, combined the organic layers, dried with anhydrous sodium sulfate, and concentrated to obtain a white solid 3-aminocoumarin (0.666g), the yield was 82.7 %. |
79% | Stage #1: N-acetylglycine With triethylamine; p-toluenesulfonyl chloride In toluene at 20℃; for 3h; Stage #2: salicylaldehyde In toluene for 2h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | With sodium acetate; In acetic anhydride; at 95℃; for 2h; | Raw material N-acetylglycine, p-methylsulfonyl benzaldehyde,Anhydrous sodium acetate is put into a 500ml four-neck bottle.Adding the reaction solvent acetic anhydride to start heating and heating, the reaction temperature is set to 95 ° C,The reaction was kept for 2 hours, and a small amount of solid in the reaction flask was not dissolved.After the end of the reaction, the solvent was removed. After the solvent was evaporated to dryness, anhydrous ethanol and purified water were added to the reaction mixture and stirred for 1 hour to remove residual acetic anhydride. After suction filtration, the obtained solid is the target product.Place the target product in an oven. The target product was obtained in an amount of 25 g, and the yield was 58percent. |
Tags: 543-24-8 synthesis path| 543-24-8 SDS| 543-24-8 COA| 543-24-8 purity| 543-24-8 application| 543-24-8 NMR| 543-24-8 COA| 543-24-8 structure
[ 150-25-4 ]
2-(Bis(2-hydroxyethyl)amino)acetic acid
Similarity: 0.74
[ 24123-14-6 ]
2-((2-Aminoethyl)amino)acetic acid
Similarity: 0.74
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P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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