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CAS No. : | 118753-66-5 |
Formula : | C9H19N3O2 |
M.W : | 201.27 |
SMILES Code : | O=C(N1CCN(N)CC1)OC(C)(C)C |
MDL No. : | MFCD08274502 |
InChI Key : | QMZFIRHRGPLKEV-UHFFFAOYSA-N |
Pubchem ID : | 22029174 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.89 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 61.3 |
TPSA ? Topological Polar Surface Area: Calculated from | 58.8 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | -0.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 0.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -0.75 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.35 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.0 |
Solubility | 20.0 mg/ml ; 0.0993 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -0.97 |
Solubility | 21.4 mg/ml ; 0.106 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.21 |
Solubility | 125.0 mg/ml ; 0.619 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 | No |
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 | -7.4 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 | 0.55 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 1.0 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) | 2.57 |
* 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% | Stage #1: With acetic acid; zinc In methanol at 0 - 20℃; for 2 h; Stage #2: With sodium hydrogencarbonate In methanol; water | To a solution of the compound obtained in the above step (1) (730 mg) in methanol (10 mL) was added zinc powder (1.1 g) at room temperature and thereto was added dropwise acetic acid (10 mL) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered and to the filtrate was added an aqueous sodium hydrogencarbonate solution to basify. After stirring, the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to obtain l-amino-4-tert- butoxycarbonylpiperazine (730 mg, yield: 100 percent) as a pale yellow oil. |
58% | With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 25℃; for 12 h; | To a solution of 1 ,1 -dimethylethyl 4-nitroso-1 -piperazinecarboxylate (500 mg, 2.33 mmol) in THF (23 mL) at O0C was added dropwise a solution of LAH (5.8 mL, 5.8 mmol, 1 M in THF). The reaction mixture warmed to 25°C over 12h and was subsequently quenched by dropwise addition of a saturated solution of potassium sodium tartrate. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4) and concentrated at 250C yielding a yellow oil that was used without further purification (270 mg, 58percent): LCMS (ES) m/e 202 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With benzotriazol-1-ol; 1,2-dichloro-ethane; In dichloromethane; N,N-dimethyl-formamide; for 12.0h; | To a solution of 1 ,1-dimethylethyl 4-amino-1 -piperazinecarboxylate (270 mg, 1.34 mmol) in DCM-DMF (4:1 , 15 ml_) were added 3-oxo-3,4-dihydro-2H-pyrido[3,2- i?][1 ,4]thiazine-6-carboxylic acid (283 mg, 1.34 mmol), EDC (250 mg, 1.61 mmol) and HOBT (217 mg, 1.61 mmol). After 12h, the solution was concentrated and the residue purified via column chromatography (silica, 1% MeOH in DCM (1% NH4OH)) yielding the title compound as a yellow foam (412 mg, 78 %): LCMS (ES) m/e 394 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16.0h; | (i) 4-Amino-piperazine-1-carboxylic acid tert-butyl ester To a solution of Piperazin-1-ylamine in 20 ml THF and 1.37 ml NEt3, 2.2 g Boc2O in 5 ml THF were added dropwise at 0 C. The reaction mixture was stirred for 16 h at RT then 50 ml ethyl acetate and 20 ml water were added. The organic layer was separated, washed with brine and dried over Na2SO4. After removal of the solvent under reduced pressure the product was obtained as a white solid. Yield: 1.53 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium chloride; hydrazine hydrate; | Step B: Tertbutyl 4-amino-1-piperazine carboxylate Under an inert atmosphere at ambient temperature, 15.3 g of the product of Step A and 80 ml of hydrazine hydrate were mixed together and then 150 ml of a saturated aqueous solution of ammonium chloride were added. Extraction was done with methylene chloride and the organic phase was washed with an aqueous solution of ammonium chloride, dried, and the solvent was eliminated under reduced pressure. After chromatography on silica (eluent:methylene chloride - methanol, 100/7) 5 g of the expected product were obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; water; | (1) <strong>[118753-66-5]4-Amino-1-tert-butoxycarbonylpiperazine</strong> (3.00 g), 4-fluoronitrobenzene (2.54 g) and N,N-diisopropylethylamine (8.82 g) were dissolved in N-methyl-2-pyrrolidone (30 mL), and the mixture was stirred at 80C for 18 hr. The reaction mixture was added to water and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give 1-tert-.butoxycarbonyl-4-(4-nitrophenyl)aminopiperidine (2.55 g) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With benzotriazol-1-ol; triethylamine; In dichloromethane; at 20℃; | To a solution of 3-carboxyl-l-(2-chlorophenyl)-5-(4-chlorophenyl)-4- EPO <DP n="52"/>methoxy-lH-pyrazole (1.96 g, compound obtained in Reference Example 1(6)) in methylene chloride (20 mL) was added l-amino-4-tert-butoxycarbonylpiperazine (730 mg, compound obtained in Reference Example 16(2)), water-soluble carbodiimide HCl (1.0 g), 1-hydroxybenzotriazole hydrate (827 mg) and triethylamine (753 muL), and the mixture was stirred at room temperature overnight. To the reaction mixture was added an aqueous sodium hydrogencarbonate solution and the mixture was stirred and extracted with chloroform. The extract was concentrated in vacuo and the crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate = 60/40 to 40/60) to obtain 3-[N-(4-tert-butoxycarbonylpiperazin-l-yl)- carbamoyl] -l-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methoxy-lH-pyrazole (1.56 g; yield: 79 %) as a colorless solid. MS(APCI)m/z; 546/548 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | To a solution of the compound obtained in the above step (1) (730 mg) in methanol (10 mL) was added zinc powder (1.1 g) at room temperature and thereto was added dropwise acetic acid (10 mL) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was filtered and to the filtrate was added an aqueous sodium hydrogencarbonate solution to basify. After stirring, the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to obtain l-amino-4-tert- butoxycarbonylpiperazine (730 mg, yield: 100 %) as a pale yellow oil. | |
96% | With ammonium chloride; zinc; In tetrahydrofuran; water; at 20℃; | To a stirred solution of tert-butyl 4-nitrosopiperazine--carboxylate (0 500 g, 2 32 mmol, 1 equiv) in THF: H20 (10: 10 mL) was added NLLCl (1.98 g, 37. 17 mmol, 16.0 equiv) and then Zn dust (1.21 g, 18.58 mmol, 8.0 equiv) was added portion wise. After completion of addition the reaction mixture was stirred at RT for overnight. Progress of the reaction was monitored by LCMS Reaction mixture was diluted with water (100 mL) and filtered off over celite bed and filtrate was extracted with DCM (100 mL c 2) Organic layer was separated and dried over anhydrous NarSCrt and concentrated under reduced pressure to obtain tert-butyl 4- aminopiperazine-l-carboxylate (0.420 g, 96 % Yield) as a yellow semi solid. LCMS 202.3 i M l l f : T-I NMR (400MHz, Chloroform-d) d 3.47 (br s , 4 H), 3.14 (br. s? 2 H), 2 56 (br. s., 4 H), 1.45 (s, 9 H). |
86% | With acetic acid; zinc; In methanol; at 0 - 20℃; for 2.0h;Inert atmosphere; | 1-Boc-4-nitrosopiperazine (1.46 g, 6.8 mmol) was dissolved in 10 mL of methanol at room temperature,Zinc powder (2.20 g, 33.8 mmol) was added, cooled to 0 C, acetic acid (20 mL) was slowly added dropwise, and then heated to room temperature under nitrogen protection and stirred for 2 hours.After the reaction was completed, the solution was filtered, and the pH was adjusted to 9-10 with a saturated sodium bicarbonate aqueous solution, and 40 mL of water was added.Extract three times with 180 mL of dichloromethane, combine the organic phases, dry over anhydrous sodium sulfate, filter,Spin-drying and purification to obtain compound 1-Boc-4-aminopiperazine (1.18 g, yield 86%) |
58% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 25℃; for 12.0h; | To a solution of 1 ,1 -dimethylethyl 4-nitroso-1 -piperazinecarboxylate (500 mg, 2.33 mmol) in THF (23 mL) at O0C was added dropwise a solution of LAH (5.8 mL, 5.8 mmol, 1 M in THF). The reaction mixture warmed to 25C over 12h and was subsequently quenched by dropwise addition of a saturated solution of potassium sodium tartrate. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried (Na2SO4) and concentrated at 250C yielding a yellow oil that was used without further purification (270 mg, 58%): LCMS (ES) m/e 202 (M+H)+. |
With acetic acid; zinc; In water; at 0℃; for 5.0h; | General procedure: To a well-stirred solution of an appropriate intermediate (7a-e) (0.10mol) in a mixed solution of AcOH (100mL) and H2O (100mL) was added zinc powder (26.2g,0.40mol) at 0C, followed by stirring for 6-8hat the same temperature. After completion of the reaction as indicated by TLC, the resulted mixture was filtered and the filtrate was concentrated under reduced pressure. Then ethyl acetate (100mL) was added and the misture was stirred for 0.5hat the room temperature. The mixture was filtered, and the filtrate was concentrated under reduced presusre to yield the corresponding intermediates 8a-e. | |
With hydrogenchloride; zinc; In methanol; water; at 0℃; for 0.5h; | (0680) In a 100 ml round-bottomed flask was added Compound 232A (0.15 g) and zinc (1 g) in water/methanol (1:1, 10 ml) to give a suspension. The mixture was cooled to 0 C. 12N Aqueous HCl (2 ml) was added slowly, and the mixture was stirred at 0 C. for 30 minutes. 2N Aqueous NaOH solution was used to adjust the mixture to basic pH. The mixture was filtered, and extracted with ether (3×30 ml). After drying over Na2SO4, filtration, and concentration, the crude product was added to a silica gel column (Analogix, SF15-12 g,) and purified by eluting with 0-25% ethyl acetate in hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(ii) 4-({1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carbonyl}-amino)-piperazine-1-carboxylic acid tert-butyl ester To a solution of 1 g 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-indole-2-carboxylic acid and 1.3 ml NEM in 8 ml DCM, 914 mg TOTU were added and the mixture was stirred for 30 min at RT. Then 673 mg <strong>[118753-66-5]4-Amino-piperazine-1-carboxylic acid tert-butyl ester</strong> were added and the reaction was stirred over night. After removal of the solvent under reduced pressure the residue was directly purified by chromatography on silica gel eluding with an ethyl acetate/heptane gradient. Yield: 1.1 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To Compound 33 prepared as in Intermediate Example 1 (8.29 g, 41.2 mmol) and pyridine (6.0 mL, 74.2 mmol) in MeCN (120 mL) was added dropwise ethyl chloroformate (5.9 mL, 61.9 mmol). The resulting mixture was stirred at room temperature for 3 h, then partitioned between EtOAc and saturated aqueous NaHCO3, dried with Na2SO4, and concentrated in vacuo to yield a residue, which was used in the next step without further purification. MS 274 (M+1)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The white solid from step A in ethanol (50 mL) was cooled to 0 C., and a pre-mixed solution of NaOCl (10-13% active chlorine, 43.4 mL) and 15% NaOH (78.0 mL) was added dropwise via an addition funnel. The ice bath was removed and the resulting mixture was stirred at room temperature for 1 h. 1N HCl was added to the resulting mixture until the pH of the solution was about pH 1, and the resulting mixture was stirred at room temperature for an additional 15 min. The pH of the solution was made basic with saturated aqueous potassium carbonate, and the resulting solution concentrated in vacuo to half the volume, then extracted three times with EtOAc, the combined organics were dried with Na2SO4, and concentrated in vacuo to yield the title compound, which was used in the next step without further purification. MS 202 (M+1)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; | Step 1. tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate (206) To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added <strong>[118753-66-5]tert-butyl 4-aminopiperazine-1-carboxylate</strong> 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4-dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give tert-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1H, m), 1.95 (2H, m), 2.38 (1H, m), 2.70 (1H, d, J=12.0 Hz), 2.76 (4H, m), 2.99 (1H, d, J=12.0 Hz), 3.30 (1H, m), 3.57 (4H, m), 3.89 (1H, d, J=8.0 Hz), 4.90 (1H, d, J=11.6 Hz), 5.04 (1H, d, J=12.0 Hz), 7.21 (5H, m), 8.90 (1H, br s). |
88% | With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; | To a solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 1 (0.17 g, 0.615 mmol) in dry DCM (10 mL) were added te/f-butyl 4-aminopiperazine-1-carboxylate 205 (0.19 g, 0.923 mmol), 1-hydroxybenzotriazole (0.125 g, 0.923 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.177 g, 0.923 mmol) and 4- dimethylaminopyridine (0.113 g, 0.923 mmol) at room temperature. The reaction mixture was stirred at room temperature overnight, and then concentrated under vacuum. The residue was purified by column chromatography to give terf-butyl 4-([(2S,5R)-6-(benzyloxy)-7-oxo- 1 ,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)piperazine-1-carboxylate 206 (0.25 g, 88%) as a clear thick oil. 1H NMR (400 MHz, CDCl3): delta 1.46 (9H, s), 1.62 (1 H, m), 1.95 (2H, m), 2.38 (1 H, m), 2.70 (1 H, d, J = 12.0Hz), 2.76 (4H, m), 2.99(1H, d, J = 12.0 Hz), 3.30 (1 H, m), 3.57 (4H, m), 3.89 (1 H, d, J = 8.0 Hz), 4.90 (1H, d, J = 11.6 Hz), 5.04 (1 H, d, J = 12.0 Hz), 7.21 (5H, m), 8.90 (1 H, br s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30 g | With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 2.0h; | [00229] Step-3: Synthesis tert-butyl 4-((6-bromo-7-fluoro-3-nitroquinolin-4- yl)amino) piperazine- 1 -carboxylate, 4: [00230] DIPEA (26.72mL, 0.15712mo1) was added to a stirred solution of 6- Bromo-4-chloro-7-fluoro-3-nitroquinoline, 9 (24g, 0.07856mo1) and <strong>[118753-66-5]tert-butyl 4-aminopiperazine-1-carboxylate</strong> (18.97g, 0.09427mo1) in DMF, 200mL at 0 00. The reaction mixture was allowed to room temperature and stirred for 2h. Reaction was monitored by TLC (30%EtOAc in hexane), after completion of reaction, diluted with water (l5OmL), the precipitated yellow solid was filtered-off, washed with water and dried under vacuum. The crude material was purified by column chromatography by using5i02 (15% EtOAc in Hexane) to afford of tert-butyl4-((6-bromo-7-fluoro-3-nitroquinolin-4- yl) amino) piperazine-1-carboxylate, 4 (30g, 81%). 1H NMR (300MHz, CDCI3): O 10.42 (5, 1H), 10.22-10.19 (d, 1H), 9.36 (5, 1H), 7.67-7.64 (d, 1H), 4.35-4.25 (t, 2H), 3.46-3.08 (t, 4H), 2.84-2.65 (t, 2H), 1.50 (5, 9H); LCMS: mlz= 469.9 (M+1) and 471.9 (M+2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium chloride; zinc; In tetrahydrofuran; water; for 0.5h; | [00227] Step-2: Synthesis of tert-butyl 4-aminopiperazine-1-carboxylate, 3:[00228] To a stirred solution of tert-butyl 4-nitropiperazine-1-carboxylate, 2 (22g, 0.09513mo1) in THF (200mL), a saturated solution of NH4CI (81.4g, 1.521mo1 in water l5OmL) was added. Zn (49.7g, 0.760mo1) was added portion wise and the resulting suspension was stirred for 30mm. The reaction was monitored by TLC (10% MeOH in DCM). The reaction mass was filtered through celite-pad and washed withDCM. The Aqueous layer was extracted with DCM (3x 200mL). The combined organic layers were washed with brine solution, dried over anhydrous Na2504 and concentrated to dryness to afford crude tert-butyl 4-aminopiperazine-1-carboxylate, 3 (18g, 83%). 1H NMR (DMSO-d6, 400MHz): O 3.29-3.19 (m, 4H), 2.55-2.62 (m, 2H), 2.45-2.38 (m, 2H), 1.38 (5, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
120 mg | With N-ethyl-N,N-diisopropylamine; In chloroform; at 20℃; for 3.0h; | (1) The compound 1 (100 mg) and diisopropylethylamine (240 mL) were dissolved in chloroform, isovaleryl chloride(217 mL) was added to the solution, and the reaction mixture was stirred for 3 hours at room temperature. Thereaction mixture was diluted with a saturated aqueous solution of sodium bicarbonate, and extracted twice withchloroform. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated underreduced pressure. The resulting residue was suspended and washed in a mixed solution of ethyl acetate-hexane,taken by filtration, and dried to give the compound 2 (120 mg) as a colorless solid.MS (APCI) 286 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16.0h; | General procedure: Chloro derivative (1 mol), amine (1 mol) and K2CO3 (2mol) were taken in DMF (10 v). The reaction mixture washeated to 100 C, stirred for 16 h. Then the reaction mixturewas cooled to room temperature, diluted with water (50 v) extracted with EtOAC (2 x 50 v). Combined organic layerswere dried over anhydrous sodium sulphate, evaporated thesolvent in vacuo. Crude products were purified by columnchromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | General procedure: To a well-stirred solution of intermediate 5 (2g, 5.6mmol) in C2H5OH(60mL) was added a drop of AcOH. The resulted mixture was refluxed for 0.5h. Then intermediates 8a (2.95g) was added, followed by stirring for 10hat the same temperature. After cooled to room temperature, The resulting solid was collected by filtration and dried to give the target compounds 9a as a light yellow solid in 82% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In ethanol; at 78℃; for 2.0h; | General procedure: To a well-stirred solution of intermediate 5a (2.0 g,5.29 mmol) in ethanol (10 mL) was added 1-amino-4-methylpiperazine 9a (0.61 g, 5.29 mmol) and a drop of acetic acid,and the mixturewas stirred at 78 C for 2 h. The mixturewas cooledto room temperature and the resulting solid was collected byfiltration and purified by column chromatography to give the targetcompounds 6a-1 as a yellow solid in 75% yield. M.p: 228-230 C; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With acetic acid; In ethanol; at 78℃; for 2.0h; | General procedure: To a well-stirred solution of intermediate 5a (2.0 g,5.29 mmol) in ethanol (10 mL) was added 1-amino-4-methylpiperazine 9a (0.61 g, 5.29 mmol) and a drop of acetic acid,and the mixturewas stirred at 78 C for 2 h. The mixturewas cooledto room temperature and the resulting solid was collected byfiltration and purified by column chromatography to give the targetcompounds 6a-1 as a yellow solid in 75% yield. M.p: 228-230 C; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With acetic acid; In ethanol; at 78℃; for 2.0h; | General procedure: To a well-stirred solution of intermediate 5a (2.0 g,5.29 mmol) in ethanol (10 mL) was added 1-amino-4-methylpiperazine 9a (0.61 g, 5.29 mmol) and a drop of acetic acid,and the mixturewas stirred at 78 C for 2 h. The mixturewas cooledto room temperature and the resulting solid was collected byfiltration and purified by column chromatography to give the targetcompounds 6a-1 as a yellow solid in 75% yield. M.p: 228-230 C; |
Tags: 118753-66-5 synthesis path| 118753-66-5 SDS| 118753-66-5 COA| 118753-66-5 purity| 118753-66-5 application| 118753-66-5 NMR| 118753-66-5 COA| 118753-66-5 structure
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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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