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CAS No. : | 17794-48-8 |
Formula : | C10H8F3NO3 |
M.W : | 247.17 |
SMILES Code : | O=C(O)CNC(C1=CC=CC(C(F)(F)F)=C1)=O |
MDL No. : | MFCD00029782 |
InChI Key : | ZDGGJQMSELMHLK-UHFFFAOYSA-N |
Pubchem ID : | 2777432 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 51.02 |
TPSA ? Topological Polar Surface Area: Calculated from | 66.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 2.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 2.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | 1.78 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 1.93 |
Log S (ESOL):? ESOL: Topological method implemented from | -2.63 |
Solubility | 0.576 mg/ml ; 0.00233 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (Ali)? Ali: Topological method implemented from | -3.14 |
Solubility | 0.181 mg/ml ; 0.000733 mol/l |
Class? Solubility class: Log S scale | Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -3.07 |
Solubility | 0.211 mg/ml ; 0.000853 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.31 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.56 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.52 |
* 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 |
---|---|---|
95% | A 12-L 4-neck round bottom flask equipped with a thermocouple controller, mechanical stirrer, heating mantle, condenser and a nitrogen in/outlet adapter was charged with gycine (1, Alfa Aesar) (318 g; 4.19 mol), acetonitrile (1.2 L), and a solution of sodium hydroxide (5.31 L; 10.62 mo) and the mixture was cooled to 4 C. with stirring. A solution of 3-(trifluoromethyl)benzoyl chloride (2, Alfa Aesar) (885.0 g; 4.12 mol) (640 mL) in acetonitrile (0.75 L) (total 1.39 L) was added dropwise over 2 h while the internal temperature was maintained between 4-6 C., and the slightly orange-pinkish solution was stirred at 4 C. for an additional 30 min. The reaction was acidified to pH=3 with conc. 37% HCl solution (400 mL added over 30 min) at 0-6 C., and stirred for 1 h at 0 C. (until a slightly yellowish suspension resulted). The solid was collected by filtration, washed with cold (0 C.) deionized ("D.I") H2O (300 mL*2), dried under air-suction for 2 h, and then placed in a drying oven at 60 C. under house vacuum (120 mmHg) for 20 h to afford pure 3 as an off-white solid. The filtrate was extracted with EtOAc (1 L*2), and the combined organic phases washed with brine (300 mL), and concentrated at 66 C. under house vacuum and then high vacuum (20 mmHg) to give crude product as an off-white waxy solid, which was triturated and sonicated with toluene (1 L) and stirred at 10 C. for 1 h. The resulting solid was collected by filtration, washed with hexanes (50 mL*2), dried in an vacuum oven at 50 C. under house vacuum to afford additional pure title compound, 3, as an off-white solid. The structure of 3 was confirmed with its 1H-NMR. | |
91% | With hydrogenchloride; sodium hydroxide; In acetonitrile; at 0 - 3℃; for 1h;pH 2 - 3; | Manufacturing example 1: (3-trifluoromethylbenzoylamino)-acetic acid [Show Image] Glycine 0.763 g (10.16 mmol) were suspended in acetonitrile 20 ml and 2 M NaOH aqueous solution 12.7 ml (25.40 mmol, 2.5 eq.) were also added. After chilling at 0-3C, 2.12 g (10.16 mmol, 1.0 eq.) of 3- (trifluoromethyl) -benzoyl chloride were diluted with 4 ml acetonitrile and added dropwise slowly to reaction mixture. After one hour agitation at the same temperature, pH was controlled to 2 to 3 with 3N hydrochloric acid aqueous solution. After keeping upright at room temperature, upper organic solution was separated, and lower aqueous solution was extracted with ethylacetate three times. Those organic solutions obtained as described above were brought all together, dried with anhydrous magnesium sulfate and concentrated, removing the solvent under decompression. Residues were solidified with toluene, filtered, washed with normal hexane and 2.28 g (91%) target compound as white solid were yielded. 1H NMR(400MHz,DMSO-d6) 3.94(2H,d), 7.74(1H,t), 7.93(1H,d), 8.16(1H,d), 8.20(1H,s), 9.12(1H,t) |
91% | With hydrogenchloride; sodium hydroxide; In water; acetonitrile; at 0 - 3℃; for 1h;pH 2 - 3; | Manufacturing Example 1 (3-trifluoromethylbenzoylamino)-acetic acid Glycine 0.763 g (10.16 mmol) was suspended into acetonitrile 20 ml and 2M NaOH aqueous solution 12.7 ml (25.40 mmol, 2.5 eq.) was also added. After chilling at 0-3 C., 2.12 g (10.16 mmol, 1.0 eq.) of 3-(trifluoromethyl)-benzoyl chloride was diluted with 4 ml acetonitrile and was added dropwise slowly to reaction mixture. After one hour agitation at same temperature, pH was controlled to 2 to 3 with 3N hydrochloric acid aqueous solution. After keeping upright at room temperature, upper organic solution was separated, and lower aqueous solution was extracted with ethylacetate three times. Those organic solution obtained as above was brought all together, dried with anhydrous magnesium sulfate and concentrated removing its solvent under decompression. Residues was solidified with tolene, filtered, washed with normal hexane and 2.28 g (91%) target compound as white solid was yielded. 1H NMR (400 MHz, DMSO-d6) 3.94 (2H, d), 7.74 (1H, t), 7.93 (1H, d), 8.16 (1H, d), 8.20 (1H, s), 9.12 (1H, t) |
90% | (3-Trifluoromethyl-benzoylamino)acetic acid. To a rapid stirring solution of glycine (15.014 g, 0.20 mol) in MeCN (400 mL) and 2 M NaOH (250 mL) at 0 C. was slowly added a solution of 3-(trifluoromethyl)-benzoyl chloride (41.714 g, 0.20 mol) in 75 mL of MeCN over 30 min. The cloudy yellow solution was stirred at 0 C. for 30 min. The reaction mixture was acidified with 3 M HCl to pH=3, followed by removal of MeCN on rotary evaporator. The resulting mixture was then extracted with EtOAc (400 mL×3). The combined organic layers were dried, filtered and concentrated to give a light yellow solid (48.53 g), which was triturated with toluene (500 mL). After filtration, the solid product was washed with cold toluene until the filtrate was colorless. After dried under high vacuum over the weekend, a white powder product: 44.60 g (90%) was afforded. MS (M+H+)=248.1. 1H NMR (DMSO-d6) delta 12.70 (br s, 1 H), 9.17 (m, 1H), 8.20 (dd, 2H), 7.94 (dd, 1H), 7.78 (m, 1H), 3.97 (d, 2H). | |
90% | Step A(3-Trifluoromethyl-benzoylamino)acetic acid. To a rapid stirring solution of glycine (15.014 g, 0.20 mol) in MeCN (400 mL) and 2 M NaOH (250 mL) at 0 C was slowly added a solution of 3-(trifluoromethyl)-benzoyl chloride (41.714 g, 0.20 mol) in 75 mL of MeCN over 30 min. The cloudy yellow solution was stirred at 0 C for 30 min. The reaction mixture was acidified with 3 M HCI to pH = 3, followed by removal of MeCN on rotary evaporator. The resulting mixture was then extracted with EtOAc (400 mL x 3). The combined organic layers were dried, filtered and concentrated to give a light yellow solid (48.53 g), which was triturated with toluene (500 mL). After filtration, the solid product was washed with cold toluene until the filtrate was colorless. After dried under high vacuum over the weekend, a white powder product: 44.60 g (90%) was afforded. MS (M+H+) = 248.1. 1H NMR (DMSO-d6) delta 12.70 (br s, 1 H), 9.17 (m, 1 H), 8.20 (dd, 2H), 7.94 (dd, 1 H), 7.78 (m, 1 H), 3.97 (d, 2H). | |
With sodium hydroxide; | PREPARATION 1 Synthesis of N-(3-trifluoromethylbenzoyl)aminoacetic acid 5.5 of 3-trifluoromethylbenzoyl chloride were dropped slowly onto 15 ml of an aqueous solution containing 2.0 g of glycine and 2.1 g of sodium hydroxide, and then, after the dropwise addition was complete, the reaction solution was heated at 70 C. for 2 hours, with stirring. The mixture was allowed to stand to cool, and then the reaction solution was washed with ethyl acetate, the aqueous layer was neutralized with 8N hydrochloric acid, and the crystals which separated out were filtered to afford 4.6 g of the title compound, after drying. | |
With sodium hydroxide; at 20℃; for 4h; | Add 10 mL of 10% NaOH solution to a 50 mL three-necked flask, add 0.75 g of glycine to dissolve, slowly add 2.14 g of m-trifluoromethylbenzoyl chloride, stir at room temperature for 4 h, adjust the pH to 1-2 with hydrochloric acid, and precipitate a white solid. The ethyl acetate was recrystallized and purified to carry out the next condensation reaction.Take compound VII 1.0mmol, prepared carboxylic acid 1.0mmol in 20mL CH2Cl2, temperatureControl about 0 C, add 1.2 mmol EDCI, 2.0 mmol DIPEA, 1.2 mmol HOBt, then stir at room temperature overnight. The reaction solution was washed with 10 mL 5% HCl solution, 10 mL 5% NaHCO3 solution, 10 mL saturated brine. After two times, it was dried over anhydrous Na 2 SO 4 and then dried. White solid, yield 63%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Trans-4-aminocyclohexanol hydrochloride (500 mg) was dissolved DMF (11 mL) prior to the addition of <strong>[17794-48-8](3-trifluoromethyl-benzoylamino)-acetic acid</strong> (815.0 mg) and 4-methylmorpholine (1.0 mL). After 5 min, BOP reagent (1.4 g) was added and the reaction was stirred overnight. Ethyl acetate was added, and the solution was washed with brine, 1N HCl, and saturated NaHCO3. The desired (trans)-N-[(4-hydroxy-cyclohexylcarbamoyl)-methyl]-3-trifluoromethyl-benzamide (480.5 mg) was then collected as a solid. MS found: (M+H)+=345.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N,N-diethyl-N-isopropylamine; (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In DMF (N,N-dimethyl-formamide); dichloromethane; at 20℃; for 12h; | Step 3 A sample of [(1R,3R,4S)-4-amino-3-(3-methyl-butyl)-cyclohexyl]-carbamic acid tert-butyl ester (50 mg, 0.18 mmol) was dissolved in 1:1 CH2Cl2/DMF (2 mL). The resultant solution was charged successively with N,N-diethylisopropylamine (0.16 mL, 0.9 mmol), <strong>[17794-48-8](3-trifluoromethyl-benzoylamino)-acetic acid</strong> (47 mg, 0.19 mmol, prepared as described in WO PCT 0250019), and BOP (116 mg, 0.26 mmol). The reaction was stirred for 12 h at RT and then partitioned between EtOAc and sat. NaHCO3; the aqueous phase was back extracted with EtOAc (1*). The organic phases were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography afforded {(1R, 3R,4S)-3-(3-methyl-butyl)-4-[2-(3-trifluoromethyl-benzoylamino)-acetylamino]-cyclohexyl}-carbamic acid tert-butyl ester (33 mg). MS found: (M+H)+=514.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 2.75h; | Step 3 A solution of tert-butyl (1R,3R,4S)-4-amino-3-(methoxymethyl)cyclohexylcarbamate (45 mg, assumed 0.163 mmol) in acetonitrile (1.5 mL) was treated sequentially with <strong>[17794-48-8]2-(3-(trifluoromethyl)benzamido)acetic acid</strong> (43 mg, 0.174 mmol, see PCT WO 0250019), diisopropylethylamine (61 muL, 0.348 mmol) and TBTU (62 mg, 0.192 mmol). The mixture was stirred at rt for 2.75 h, then was diluted with ethyl acetate, washed sequentially with 1.0 M aqueous HCl, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluding with 1:3 v/v hexane-ethyl acetate, to provide tert-butyl (1R,3R,4S)-3-(methoxymethyl)-4-(2-(3-(trifluoromethyl)benzamido)acetamido)cyclohexylcarbamate as a white solid (48 mg). MS found: (M+H)+=488.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 0 - 20℃; | (8a) (2S, 3S)-(2-Amino-3-hydroxy-hex-4-ynyl)-carbamic acid benzyl ester (2.53 g, prepared as in WO PCT 0250019) was dissolved in CH2Cl2 (50 ml) and 4-methylmorpholine (2.53 ml) and cooled to 0 C. prior to the addition of <strong>[17794-48-8](3-trifluoromethyl-benzoylamino)-acetic acid</strong> (1.49 g) and HATU (2.23 g). After the reaction was stirred overnight at room temperature, the CH2Cl2 was removed and EtOAc was added. The organic layer was washed with saturated NH4Cl solution (aq) brine, dried, filtered, and concentrated. Flashed chromatography of the resulting residue gave (2S, 3S)-{3-hydroxy-2-[2-(3-trifluoromethyl-benzoylamino)-acetylamino]-hex-4-ynyl}-carbamic acid benzyl ester (1.3 g). MS found: (M+H)+=492.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In DMF (N,N-dimethyl-formamide); dichloromethane; | A sample of (1s,4s)-4-(aminomethyl)-N,N-dibenzylcyclohexanamine (0.475 g) was taken through the procedure of Example 1h, Step 1 to give (1s,4s)-N,N-dibenzyl-4-((isopropyl(methyl)amino)methyl)cyclohexanamine (280 mg). This material was hydrogenated according to the procedure of Example 1h, Step 4 to give (1s,4s)-4-((isopropyl(methyl)amino)methyl)cyclohexanamine. The entirety of this sample (95 mg) was dissolved in methylene chloride (5 mL) and DMF (2 mL). The resultant solution was charged successively with <strong>[17794-48-8](3-trifluoromethyl-benzoylamino)-acetic acid</strong> (127 mg), PyBOP (268 mg), and triethylamine (0.14 mL). The mixture was stirred overnight and diluted with methylene chloride before being washed with water thrice. The organic phase was then washed with sat. sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated in vacuo. The residue was purified by RP-HPLC to afford the title compound as an oil (5 mg). MS found: (M+H)+=414. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; HATU; In dichloromethane; at 0 - 20℃; | (8a) (2S, 3S)- (2-AMINO-3-HYDROXY-HEX-4-YNYL)-CARBAMIC acid benzyl ester (2.53 g, prepared as in WO PCT 0250019) was dissolved in CH2CL2 (50 ml) and 4-methylmorpholine (2.53 ml) and cooled to 0 C prior to the addition of (3- TRIFLUOROMETHYL-BENZOYLAMINO)-ACETIC acid (1.49 g) and HATU (2.23 g). After the reaction was stirred overnight at room temperature, the CH2CL2 WAS removed and EtOAc was added. The organic layer was washed with saturated NH4Cl solution (aq) brine, dried, filtered, and concentrated. Flashed chromatography of the resulting residue gave (2S, 3S)- {3-HYDROXY-2- [2- (3-TRIFLUOROMETHYL-BENZOYLAMINO)- ACETYLAMINO]-HEX-4-YNYL}-CARBAMIC acid benzyl ester (1.3 g). MS found : (M+H) + = 492. 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In DMF (N,N-dimethyl-formamide); at 0 - 20℃; | tert-Butyl [(3S)-1-([3-(Trifluoromethyl)benzoyl]amino}acetyl)pyrrolidin-3-yl]carbamate. To a solution of the carboxylic acid (2.7 g, 11 mmol) from step A and tert-butyl (3S)-pyrrolidin-3-ylcarbamate (2.0 g, 11 mmol) in DMF (30 mL) cooled in an ice bath was added BOP (5 g, 11 mmol) followed by triethylamine (3 mL, 22 mmol). The mixture was allowed to warm to temperature and stirred overnight. Ethyl acetate (150 mL) was added. The resulting solution was washed with NaHCO3 and brine each three times, dried over MgSO4 and concentrated. Chromatography on silica gel eluting with EtOAc provided 4.4 g (96%) of the desired product. MS (M-Boc+H)+ 316. |
96% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃;cooling with ice; | Step BBocHN'tert-Butyl [(3S)-1 -([3-(Trifluoromethyl)benzoyl]amino}acetyl)pyrrolidin-3-yl]carbamate. To a solution of the carboxylic acid (2.7 g, 1 1 mmol) from step A and tert-butyl (3S)-pyrrolidin-3-ylcarbamate (2.0 g, 1 1 mmol) in DMF (30 mL) cooled in an ice bath was added BOP (5 g, 1 1 mmol) followed by triethylamine (3 mL, 22 mmol). The mixture was allowed to warm to temperature and stirred overnight. Ethyl acetate (150 mL) was added. The resulting solution was washed with NaHC03 and brine each three times, dried over MgS04 and concentrated. Chromatography on silica gel eluting with EtOAc provided 4.4 g (96%) of the desired product. MS (M-Boc+H)+ 316. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h; | (3R,5R)-5-Methylpyrrolidin-3-ol hydrochloride (1.80 g, 13 mmol) was dissolved in dichloromethane (50 mL) and diisopropylethylamine (2.1 mL, 12.0 mmol) under nitrogen. (3-Trifluoromethyl-benzoylamino)-acetic acid (2.93 g, 11.85 mmol) was added followed by EDC (3.41 g, 17.8 mmol) and the mixture was stirred at room temperature for four hours. The mixture was diluted with NH4Cl/H2O and extracted twice with ethyl acetate. The combined extracts were washed with NaHCO3/H2O and brine, dried over MgSO4, filtered and concentrated to give a dark orange oil. Chromatography on silica gel eluting with ethyl acetate to 5% methanol/ethyl acetate gave the coupled product as a pale orange solid, 3.19 g (81%, 2 steps). LC/MS (M+H)+ m/z=331.1. 1H NMR (CDCl3, major rotamer) delta 8.12 (s, 1H), 8.01 (d, 1H), 7.76 (d, 1H), 7.57 (t, 1H), 7.50 (m, 1H), 4.56 (m, 1H), 4.34 (m, 1H), 4.23 (m, 1H), 4.11 (m, 1H), 3.61 (dd, 1H), 3.51 (d, 1H), 2.71 (d, 1H), 2.17 (m, 1H), 1.81 (m, 1H), 1.32 (d, 3H). |
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 4h;Inert atmosphere; | Step GN-{2-[(2f?,4f?)-4-Hydroxy-2-methylpyrrolidin-1 -yl]-2-oxoethyl}-3-(trifluoro- methyl)benzamide. (3f?,5f?)-5-Methylpyrrolidin-3-ol hydrochloride (1.80 g) was dissolved in dichloromethane (50 mL) and diisopropylethylamine (2.1 mL, 12.0 mmol) under nitrogen. (3- Trifluoromethyl-benzoylamino)-acetic acid (2.93 g, 1 1.85 mmol) was added followed by EDC (3.41 g, 17.8 mmol) and the mixture was stirred at room temperature for four hours. The mixture was diluted with NH4CI/H20 and extracted twice with ethyl acetate. The combined extracts were washed with NaHC03/H20 and brine, dried over MgS04, filtered and concentrated to give a dark orange oil. Chromatography on silica gel eluting with ethyl acetate to 5% methanol/ethyl acetate gave the coupled product as a pale orange solid, 3.19 g (81 %, 2 steps). LC/MS (M+H)+ m/z = 331 .1. 1H NMR (CDCI3, major rotamer) delta 8.12 (s, 1 H), 8.01 (d, 1 H), 7.76 (d, 1 H), 7.57 (t, 1 H), 7.50 (m, 1 H), 4.56 (m, 1 H), 4.34 (m, 1 H), 4.23 (m, 1 H), 4.1 1 (m, 1 H), 3.61 (dd, 1 H), 3.51 (d, 1 H), 2.71 (d, 1 H), 2.17 (m, 1 H), 1.81 (m, 1 H), 1.32 (d, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 4.5h;Heating / reflux; | (2S,4R)-4-(Benzyloxy)-2-isopropylpyrrolidine (0.410 g, 1.90 mmol) was dissolved in dichloromethane (30 mL) under nitrogen. (3-Trifluoromethylbenzoylamino)-acetic acid (0.462 g; 1.90 mmol) was added followed by EDC (0.394 g, 2.06 mmol) and the mixture was stirred at room temperature-overnight. LC/MS revealed the reaction was not yet complete. More (3-Trifluoromethyl-benzoylamino)-acetic acid (0.12 g, 0.48 mmoles) and more EDC (0.30 g, 1.6 mmoles) were added and stirring continued for 3 hours at room temperature, then at reflux for 1.5 hours. The mixture was chromatographed on silica gel eluting with 30% ethyl acetate/hexane to provide 0.66 g (79%) of the coupled product as a colorless oil. LC/MS (M+H)+ m/z=449.2; 1H NMR (CDCl3) delta 8.03 (m, 1H), 7.76 (m, 1H), 7.58 (m, 2H), 7.34 (m, 5H), 4.52 (m, 2H), 4.03-4.34 (m, 4H), 3.65 (m, 1H), 3.48 (m, 1H), 2.54 (m, 1H), 2.12 (m, 1H), 1.92 (m, 1H), 0.92 (d, 3H), 0.77 (d, 3H). |
79% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;Inert atmosphere; Reflux; | Step FN-{2-[(2S,4f?)-4-Benzyloxy-2-isopropylpyrrolidin-1-yl]-2-oxoethyl}-3- (trifluoromethyl)benzamide. (2S,4f?)-4-(Benzyloxy)-2-isopropylpyrrolidine (0.410 g, 1 .90 mmol) was dissolved in dichloromethane (30 mL) under nitrogen. (3-Trifluoromethyl- benzoylamino)-acetic acid (0.462 g, 1 .90 mmol) was added followed by EDC (0.394 g, 2.06 mmol) and the mixture was stirred at room temperature overnight. LC/MS revealed the reaction was not yet complete. More (3-Trifluoromethyl-benzoylamino)-acetic acid (0.12 g, 0.48 mmoles) and more EDC (0.30 g, 1 .6 mmoles) were added and stirring continued for 3 hours at room temperature, then at reflux for 1 .5 hours. The mixture was chromatographed on silica gel eluting with 30% ethyl acetate/hexane to provide 0.66 g (79%) of the coupled product as a colorless oil. LC/MS (M+H)+ m/z = 449.2; 1H NMR (CDCI3) delta 8.03 (m, 1 H), 7.76 (m, 1 H), 7.58 (m, 2H), 7.34 (m, 5H), 4.52 (m, 2H), 4.03-4.34 (m, 4H), 3.65 (m, 1 H), 3.48 (m, 1 H), 2.54 (m, 1 H), 2.12 (m, 1 H), 1 .92 (m, 1 H), 0.92 (d, 3H), 0.77 (d, 3H). |
Tags: 17794-48-8 synthesis path| 17794-48-8 SDS| 17794-48-8 COA| 17794-48-8 purity| 17794-48-8 application| 17794-48-8 NMR| 17794-48-8 COA| 17794-48-8 structure
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Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
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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