Structure of 4-Nitro-L-phenylalanine
CAS No.: 949-99-5
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 949-99-5 |
Formula : | C9H10N2O4 |
M.W : | 210.19 |
SMILES Code : | N[C@@H](CC1=CC=C([N+]([O-])=O)C=C1)C(O)=O |
MDL No. : | MFCD00051221 |
InChI Key : | GTVVZTAFGPQSPC-QMMMGPOBSA-N |
Pubchem ID : | 13706 |
GHS Pictogram: |
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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 | 2.0 |
Molar Refractivity | 54.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
109.14 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.84 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.55 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-2.14 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.39 |
Solubility | 86.1 mg/ml ; 0.41 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.55 |
Solubility | 59.8 mg/ml ; 0.284 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.25 |
Solubility | 11.7 mg/ml ; 0.0558 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 |
-8.47 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) |
2.03 |
* 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 |
---|---|---|
87% | With barium sulfate; hydrogen; palladium; | To a solution of Ap, a mixture of 8 g L-4-nitrophenylalanine (38 mmol) and 0.8 g barium sulfate was put in a 250 mL three-necked flask while adding the gas of hydrogen to do the hydrogenation for 4 h. The reaction mixture was filtered and concentrated to crystallization. The productions were washed with water, dried and evaporated. Finally, we added 5.9 g white powder and the yield was 87%(Fig. 1F) [19]. |
85% | With rosenmund catalyst; hydrogen; In water; at 20℃; for 3h; | A mixed solution of concentrated HNO3 (60%) and concentrated H2SO4 (1.4:1.1 v/v) was prepared and chilled to 10 C. Then, a portion of this solution (3.5 mL) was added dropwise under stirring to a solution of L-phenylalanine (4.139 g, 25.1 mmol) in H2SO4 (98%, 12.5 mL). The reaction mixture was stirred at 10 C for 2.5 h. The reaction solution was then adjusted to pH 5 with NH4OH. The pale yellow precipitate formed was collected by filtration, washed with a small volume of water and CH3CN, and then dried to yield 4-nitro-L-phenylalanine as a yellow powder (4.748 g, 90%). 4-Nitro-L-phenylalanine (2.006 g, 9.54 mmol) was suspended in water (35 mL) and subjected tohydrogenation at room temperature for 3 h in the presence of 0.2 g of 5% palladium-barium sulfate.The catalyst was filtered through a Celite pad, and the pale brown filtrate was concentrated. Theresidue was washed with CH3CN to afford a pale brown mass (1.460 g, 85%). No further purificationwas performed for the following step. The 4-amino-L-phenylalanine derivative (0.060 g, 0.33 mmol)was dissolved in 6N HCl (4 mL). Sodium nitrate in water (0.030 g/0.5 mL) was added at 0 C. Thereaction mixture was stirred at the same temperature for 40 min and diluted with 6N HCl (0.25 mL).Subsequently, sodium azide in water (0.033 g/0.75 mL) was added at 0 C. The reaction mixture wasstirred at same temperature for 5 min, and then warmed to room temperature for 1 h, thenconcentrated. The residue was reprecipitated from CH3CN to afford a pure colorless amorphous mass(0.0435 g, 64%). Analytical and spectroscopic data were identical to those reported in the literature [10]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium hydroxide; In water; acetonitrile; at 20℃; for 3h; | A solution of 80 mL of acetonitrile was added to a suspension of 37.7 g (0.179 mol) of acid 2a and 2b in 200 mL of 2% NaOH aqueous solution until complete dissolution. A solution of 61.8 g (0.183 mol) of suspension of Fmoc-OSu in 100 mL of acetonitrile was added to this solution. The reaction mixture was stirred for 3 hours at room temperature and acidified with 5% HCl to pH 4-5. The precipitated white crystals were filtered off, washed with ethyl acetate, and dried. The reaction product was recrystallized from ethanol-dioxane mixture, 50 : 50. Yield 67% (3a), 71% (3b). mp 230C (mp 233-234C [10]). IR spectrum nu, cm-1: 3429, 3202, 1724, 1693, 1601, 1520, 1447, 1354, 1223, 1057, 856, 760, 741. 1 NMR spectrum (DMSO-d6), delta, ppm: 2.90-3.09 m (1H, CH2), 3.25 d.d (1H, CH2, 2J 13.7, 3J 4.3 Hz), 4.13-4.34 m (4H, 2CH2, 2CH), 7.23-7.45 m (4Harom), 7.54 d (2Harom, 3J 8.6 Hz), 7.60-7.64 m (2Harom), 7.79 d (1H, NH, 3J 8.6 Hz), 7.88 d (2Harom, 3J 7.5 Hz ), 8.14 d (2Harom, 3J 8.6 Hz ), 12.93 s (1H, COOH). 13 NMR spectrum (DMSO-d6), delta, ppm: 36.62 (CH2), 47.03 (CH), 55.25 (CH), 66.03 (CH2), 120.56, 123.69, 125.62, 127.45, 128.07, 130.94, 141.16, 144.20, 146.73 (arom), 156.39 (CONH), 173.27 (COOH). Mass spectrum (ESI), m/z: 455.1214 [M + Na]+. C24H20N2O6. Calculated M 432.1321. |
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