Boc-Lys(Boc)-OH | (S)-2,6-Bis((tert-butoxycarbonyl)amino)hexanoic acid | Carbamates

CAS No. :	2483-46-7
Formula :	C₁₆H₃₀N₂O₆
M.W :	346.42
SMILES Code :	O=C(O)[C@@H](NC(OC(C)(C)C)=O)CCCCNC(OC(C)(C)C)=O
MDL No. :	MFCD00038515
InChI Key :	FBVSXKMMQOZUNU-NSHDSACASA-N
Pubchem ID :	7349648

Safety of [ 2483-46-7 ]

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

Computational Chemistry of [ 2483-46-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	24
Num. arom. heavy atoms	0
Fraction Csp3	0.81
Num. rotatable bonds	13
Num. H-bond acceptors	6.0
Num. H-bond donors	3.0
Molar Refractivity	89.83
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	113.96 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.87
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	2.33
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.66
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.	1.46
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	1.34
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.13

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.6
Solubility	0.875 mg/ml ; 0.00253 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.	-4.36
Solubility	0.015 mg/ml ; 0.0000434 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-2.79
Solubility	0.566 mg/ml ; 0.00163 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	No
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	Yes
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	Yes
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.	-6.76 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	1.0
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	1.0 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)	3.44

Application In Synthesis of [ 2483-46-7 ]

* 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 [ 2483-46-7 ]

[ 2483-46-7 ] Synthesis Path-Downstream 1~12

1
[ 908094-01-9 ]
[ 2483-46-7 ]
[ 2483-48-9 ]

References: [1]Journal of the American Chemical Society,1965,vol. 87,p. 611 - 619.

2
[ 2483-46-7 ]
[ 74-88-4 ]
[ 2483-48-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium carbonate; In ethyl acetate; N,N-dimethyl-formamide; at 10 - 20℃; for 5h;Inert atmosphere;	Example 2 Boc-L-Lys(Boc)-OMe A 1 L three-neck flask equipped with addition funnel, nitrogen inlet, thermometer and mechanical stirrer was charged with a solution of Boc-L-Lys(Boc)-OH (59.37 g, 161 mmol, 94 wt % in EtOAc) in N,N-dimethylformamide (anhydrous) (300 mL). Whilst stirring, potassium carbonate (24.5 g, 177 mmol) was added, and the resulting suspension was cooled on an ice bath to an internal temperature of +10 C. Iodomethane (34.3 g, 242 mmol, 15.04 mL) was added dropwise over 30 min via the addition funnel, while keeping the internal temperature <20 C. The ice bath was removed and the reaction mixture was allowed to reach room temperature. TLC indicated complete consumption of the starting material after 4.5 h of stirring at room temperature. All volatiles were removed in vacuo, the resulting white slurry solidified on standing, and it was stored at -20 C. overnight. The resultant material was taken up in water (1 L) and sat'd. NaHCO3 (0.5 L), and then extracted with EtOAc (3500 mL). The combined organic phases were washed with dilute brine (2200 mL), brine (2100 mL), then dried over Na2SO4 and concentrated. After stripping with heptane (2200 mL), the title compound was isolated as a white solid (57.08 g, 97% yield). 1H-NMR (CDCl3): In agreement with structure. LCMS (NQAD detection): Purity >99%, mass in agreement with molecular formula (pos. m/z=361 [M+1]+, 383 [M+Na]+). Specific rotation: [α]D22=6.38 (c=1.72, CHCl3).
3 g	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h;	Potassium carbonate (1.8 g, 13.0 mmol) and methyl iodide (0.65 mL, 10.4 mmol) were added to a solution of compound la (3.0 g, 8.7 mmol) in DMF (25 mL) and stirred at room temperature for 2 h. The completeness of the reaction was confirmed by TLC analysis. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was washed with water, brine, dried over Na2SC>4 and evaporated under reduced pressure to yield 3.0 g of compound lb. LCMS: 361.1 (M+H)+.

References: [1]Patent: US2016/376618,2016,A1 .Location in patent: Paragraph 0213-0218.
[2]Tetrahedron,2003,vol. 59,p. 5837 - 5848.
[3]Patent: WO2016/142852,2016,A1 .Location in patent: Paragraph 54.

3
C₁₄H₁₈NO₄Pol [ No CAS ]
[ 2483-46-7 ]
[ 122889-11-6 ]
C₃₅H₄₉N₄O₉Pol [ No CAS ]