(R)-α-Methyl-4-nitrobenzylamine HCl | Benzene Compounds

CAS No. :	57233-86-0
Formula :	C₈H₁₁ClN₂O₂
M.W :	202.64
SMILES Code :	N[C@H](C)C1=CC=C([N+]([O-])=O)C=C1.[H]Cl
MDL No. :	MFCD00066311
InChI Key :	CZQQGVFHLSBEDV-FYZOBXCZSA-N
Pubchem ID :	16212177

Safety of [ 57233-86-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 57233-86-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.25
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	54.71
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	71.84 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.07
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.09
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.99
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.57
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.92

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.61
Solubility	0.497 mg/ml ; 0.00245 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.21
Solubility	0.126 mg/ml ; 0.00062 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.85
Solubility	2.88 mg/ml ; 0.0142 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

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) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.07 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	2.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.97

Application In Synthesis of [ 57233-86-0 ]

* 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.

Downstream synthetic route of [ 57233-86-0 ]

[ 57233-86-0 ] Synthesis Path-Downstream 1~30

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[ 57233-86-0 ]
[ 542-92-7 ]
(+)-(1S,1'R)-2-<1'-(4''-Nitrophenyl)ethyl>-2-azabicyclo<2.2.1>hept-5-ene [ No CAS ]
(-)-(1R,1'R)-2-<1'-(4''-Nitrophenyl)ethyl>-2-azabicyclo<2.2.1>hept-5-ene [ No CAS ]

References: [1]Helvetica Chimica Acta,1993,vol. 76,p. 1203 - 1215.

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[ 57233-86-0 ]
1-tert-Butyl-8-chloro-6-(2-fluoro-phenyl)-4H-2,5,10b-triaza-benzo[e]azulene-3-carbonyl chloride [ No CAS ]
<R>-(-)-(R)-8-chloro-1-(1,1-dimethylethyl)-6-(2-fluorophenyl)-N-(4-nitro-1-phenylethyl)-4H-imidazo<1,5-a><1,4>benzodiazepine-3-carboxamide [ No CAS ]

References: [1]Journal of Organic Chemistry,1993,vol. 58,p. 3285 - 3298.

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[ 159596-55-1 ]
4-{2-[(R)-1-(4-Nitro-phenyl)-ethylamino]-3,4-dioxo-cyclobut-1-enylamino}-benzonitrile [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 1187 - 1202.

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Yield	Reaction Conditions	Operation in experiment
94.38%	With sodium hydrogencarbonate; In dichloromethane; water; for 3h;	Step 1 : Synthesis of (i?)-[l-(4-Nitrophenyl)ethyl]carbamic acid t-butyl ester; (Ri3= Me)(i?)-methyl-4-nitrobenzylaminehydrochloride (50mg, 0.25mmol) was put into 25ml of flask and dissolved in the saturated solution (NaHCO3 : CH2Cl2 = 1:1). To the solution was added di-t-butyl dicarbonate (135mg, 0.60mmol), followed by stirring for 3 hours. The reacting mixture was diluted with methylene chloride, washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The obtained liquid was purified by column chromatography (n-hexane/ethyl acetate = 10/1) to yield EPO <DP n="61"/>pale yellow liquid (62.0 mg, 94.38%).[alpha]D22: -43.66(C LSS3 CHCl3);IR (NaCl, neat, cm"1): 3403, 3332, 2977, 2932, 1697, 1522, 1347; 1H NMR (400MHz, CDCl3): 8.20 (d, 2H, J=8.8Hz), 7.47 (d, 2H, J = 8.8 Hz), 4.91 (s, IH), 4.85 (s, IH), 1.46 (d, 3H, J= 6.8 Hz), 1.42 (s, 9H)
92%	With sodium hydrogencarbonate; In dichloromethane; at 25℃; for 24h;	Step 1: Preparation of (R)-tert-butyl 1-(4-nitrophenyl)ethylcarbamate (C1) (R)-1-(4-nitrophenyl)ethanamine hydrochloride salt (1.0 g, 4.9 mmol), tert-butoxycarbonyl (BOC) anhydride (1.18 g, 5.43 mmol), and 10.0 mL of 1M sodium bicarbonate solution were dissolved in DCM (15 mL) and allowed to stir at 25 C. for 24 h. The organic layer was collected, and the aqueous layer was washed with DCM. The combined organic layers were then washed with water and 0.1N HCl, dried over MgSO4, filtered, and concentrated to provide C1 as a white solid. Yield: 1.2 g, 92%. GC-MS=266. 1H NMR (500 MHz, d6-DMSO) delta: 8.15 (d, 2H), 7.56 (d, 1H), 7.52 (d, 2H), 4.68 (m, 1H), 1.32 (s, 9H), 1.27 (d, 3H).

References: [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1751 - 1755.
[2]Patent: WO2006/98554,2006,A1 .Location in patent: Page/Page column 59-60.
[3]Patent: US2009/54395,2009,A1 .Location in patent: Page/Page column 47.

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[ 13094-51-4 ]
[ 57233-86-0 ]
(S)-(-)-α-methyl-4-nitrobenzylamine hydrochloride [ No CAS ]
di-tert-butyl 4-aminobutylphosphonateN¹-tert-butoxycarbonyltryptamine [ No CAS ]
C₈₄H₁₀₉N₁₇O₂₆P₂S [ No CAS ]

References: [1]Journal of the American Chemical Society,2006,vol. 128,p. 1995 - 2004.

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Yield	Reaction Conditions	Operation in experiment
98%	With triethylamine; In dichloromethane; at 20℃;	To a stirred solution of (R or S)-alpha-METHYL-4-NITROBENZYL amine hydrochloride (203 mg, 1 mmol) in anhydrous CH2C12 (10 mL) was added triethylamine (0.28 mL, 2 mmol) at room temperature. When the reaction mixture became clear, isothiocyanate (1 mmol) was added and stirred OVERNIGNT at room temperature. The mixture was evaporated by rotary evaporator and the residue was purified by flash column chromatography on silica gel with EtOAc: hexanes as eluant to N-(4-T-BUTYLBENZYL)-N -F (1R)-1- [4- (methylsulfonylamino) phenyl] ethyl} thiourea (16-5, SU-388). 98% yield, a sticky colorless oil IH NMR (CDC13) 6 8.12 (d, 2 H, J= 8.76 Hz), 7.34 (bd, 4 H), 7.14 (d, 2 H, J= 8.0 Hz), 6.21 (bs, 2 H), 5.37 (bs, 1 H), 4.54 (M, 2 H), 1.47 (d, 3 H, J= 7. 05 HZ), 1.30 (s, 9 H)

References: [1]Patent: WO2005/3084,2005,A1 .Location in patent: Page 27; 85-86.
[2]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 6043 - 6053.

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[ 65645-32-1 ]