Structure of 201932-92-5
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CAS No. : | 201932-92-5 |
Formula : | C9H9NO5 |
M.W : | 211.17 |
SMILES Code : | O=C(OC)C1=CC=C([N+]([O-])=O)C(CO)=C1 |
MDL No. : | MFCD29762434 |
InChI Key : | UZYJUGUGWPESHO-UHFFFAOYSA-N |
Pubchem ID : | 18372008 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.67 |
TPSA ? Topological Polar Surface Area: Calculated from |
92.35 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.72 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.72 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.34 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.55 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.63 |
Solubility | 4.9 mg/ml ; 0.0232 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.24 |
Solubility | 1.22 mg/ml ; 0.00579 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.69 |
Solubility | 4.3 mg/ml ; 0.0204 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 |
-7.08 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 |
2.0 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) |
2.05 |
* 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 |
---|---|---|
With sodium periodate; In tetrahydrofuran; water; at 20℃; for 3h; | A solution of 3-methyl-4-nitro-benzoic acid methyl ester (24.99 g, 128.1 mmol) and N,N-dimethylformamide dimethyl acetal (40.0 mL, 300 mmol) was heated at 1400C for 22.5 h. After cooling to rt, the reaction mixture was concentrated and the residue was crystallized from MeOH to give a purple solid.This solid was dissolved in THF (500 mL) and water (500 mL), and sodium periodate (62.62 g, 292.8 mmol) was added followed by additional sodium periodate (15.6 g, 72.9 mmol) two hours later. After stirring at rt for an additional 1 h, the reaction mixture was filtered through Celite washing with EtOAc (2 L). The filtrate was washed with saturated NaHCO3 (600 mL) and the organic layer was dried over Na2SO4. After filtration, the filtrate was concentrated and the residue was passed through a pad of silica gel, washing with CH2Cl2/hexanes (75percent- 100percent). The filtrate was concentrated and dried to give 3-formyl-4-nitro-benzoic acid methyl ester as yellowish solid. MS (EI): cal'd 210.0 (MH+), exp 210.2 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2*250 mL), water (2*250 mL), saturated aqueous sodium bicarbonate (2*250 mL), water (2*200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2*250 mL), water (2*250 mL), saturated aqueous sodium bicarbonate (2*250 mL), water (2*200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2*250 mL), water (2*250 mL), saturated aqueous sodium bicarbonate (2*250 mL), water (2*200 mL), brine (1*200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78° C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70° C. After the addition was complete the reaction mixture was stirred at -78° C. for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65° C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2*250 mL), water (2*250 mL), saturated aqueous sodium bicarbonate (2*250 mL), water (2*200 mL), brine (1*200 mL) and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 oC. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 oC. After the addition was complete the reaction mixture was stirred at -78 oC for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 oC. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; ethyl acetate; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 °C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 °C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 l of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; water; dimethyl sulfoxide; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 l of methylene chloride was cooled to -78 °C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70 °C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 1 of ethyl acetate and 1 l of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. | |
With triethylamine; In dichloromethane; dimethyl sulfoxide; | e) Preparation of methyl 3-formyl-4-nitrobenzoate. In a 5-liter four-necked round-bottomed flask 1.5 1 of methylene chloride was cooled to -78°C. Oxalyl chloride (164 g, 1.29 moles) was added slowly, followed by dropwise addition of 202 g (2.59 moles) of dry dimethylsulfoxide in 125 mL of methylene chloride, keeping the temperature below -70°C. After the addition was complete the reaction mixture was stirred at -78 °C for 30 minutes and 273 g (1.29 moles) of previously prepared methyl 3-hydroxymethyl-4-nitrobenzoate dissolved in 250 mL of methylene chloride was added dropwise. The reaction mixture was stirred an additional 30 minutes. Triethylamine (392 g 3.88 moles) in 125 mL of methylene chloride was added dropwise keeping the temperature below -65 °C. The reaction mixture was warmed up slowly to room temperature and stirred overnight. The solvent was removed using a rotary evaporator and the resulting solid treated with a mixture of 2 1 of ethyl acetate and 11 of water. The organic phase was separated, filtered through diatomaceous earth, and washed sequentially with dilute aqueous hydrochloric acid (2x250 mL), water (2x250 mL), saturated aqueous sodium bicarbonate (2x250 mL), water (2x200 mL), brine (1x200 mL) and dried over anhydrous magnesium sultate. The solvent was removed using a rotary evaporator. The crude reaction mixture was triturated with hexane and filtered yielding 234.1 g of the expected methyl 3-formyl-4-nitrobenzoate as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.06 g | With methanol; sodium tetrahydroborate; at 0℃; for 0.333333h; | ( RS-3-49) Methyl 3-formyl-4-nitrobenzoate (1.20 g, 5.73 mmol) was dissolved in MeOH (10 mL) and cooled to 0 °C. Sodium borohydride (69 mg, 1.72 mmol) was added in one portion, and the reaction mixture was stirred for 20 minutes. The reduction was quenched with 1 N HC1 (10 mL) and the methanol portion evaporated in vacuo. The aqueous phase was extracted with CH2C12 (3 chi 10 mL) to afford 1.06 g of benzylic alcohol, which was used without further purification . |
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