16413-71-1|N,N-Dimethyl-1-(naphthalen-1-yl)methanamine| Ambeed

CAS No. :	16413-71-1
Formula :	C₁₃H₁₅N
M.W :	185.27
SMILES Code :	CN(C)CC1=C2C=CC=CC2=CC=C1
MDL No. :	MFCD05124184
InChI Key :	PTKSORMJFKONON-UHFFFAOYSA-N
Pubchem ID :	264953

Safety of [ 16413-71-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P280-P305+P351+P338-P310

Computational Chemistry of [ 16413-71-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	14
Num. arom. heavy atoms	10
Fraction Csp3	0.23
Num. rotatable bonds	2
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	61.42
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	3.24 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.56
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	3.09
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.75
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.	3.12
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	2.91
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.89

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.33
Solubility	0.0863 mg/ml ; 0.000466 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.	-2.83
Solubility	0.277 mg/ml ; 0.00149 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	-4.59
Solubility	0.00477 mg/ml ; 0.0000258 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	Yes
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	Yes
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.	-5.24 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	2.0
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	0.0 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)	1.0

Application In Synthesis of [ 16413-71-1 ]

* 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.

Upstream synthesis route of [ 16413-71-1 ]
Downstream synthetic route of [ 16413-71-1 ]

[ 16413-71-1 ] Synthesis Path-Upstream 1~19

1
[ 68-12-2 ]
[ 86-52-2 ]
[ 16413-71-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With NHC-Pd(II)-Im; sodium hydroxide In water at 50℃; for 3 h; Inert atmosphere; Schlenk technique	General procedure: Under a N₂ atmosphere, NaOH (3.0 equiv), NHC-Pd(II)-Im complex 1 (1.0 molpercent), water (1.0 mL), benzyl chloride 2a (0.8 mmol), and N-formylmorpholine 3a (2.0 equiv) were successively added into a Schlenk reaction tube. The mixture was stirred at 50 °C for 3 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc, washed with brine, and dried over anhydrous Na₂SO₄. Then the solvent was removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 5:1) to give the pure products 4a. Dimethyl-naphthalen-1-yl-methyl-amine (4t):²⁴ Colourless liquid; 1H NMR (300 MHz): δ 8.24 (d, J = 7.8 Hz, 1H), 7.83–7.75 (m, 2H), 7.51–7.36 (m, 4H), 3.79 (s, 2H), 2.27 (s, 6H); 13C NMR (75 MHz): δ 134.6, 133.8, 132.4, 128.4, 127.9, 127.4, 125.9, 125.5, 125.0, 124.4, 62.4, 45.6.
91%	With potassium hydroxide In water at 80℃; for 3 h; Green chemistry	General procedure: KOH (2.4mmol), H₂O (1.0mL), (pseudo)halides 1 (0.8mmol), and formamides 2 (1.6mmol) were successively added into a reaction tube. Then the reaction mixture was stirred under the conditions shown in Tables 1–5. After the reactions were completed, the mixture was extracted by ethyl acetate, dried over anhydrous Na₂SO₄, filtered, concentrated under reduced pressure, and purified by flash chromatography to give products 3.

References: [1] Journal of Chemical Research, 2013, vol. 37, # 10, p. 611 - 614.
[2] Tetrahedron, 2014, vol. 70, # 4, p. 880 - 885.

2
[ 506-59-2 ]
[ 66-77-3 ]
[ 16413-71-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: With sodium acetate; sodium tris(acetoxy)borohydride; acetic acid In tetrahydrofuran for 12 h; Stage #2: With sodium hydrogencarbonate In dichloromethane; water	To 1-naphthaldehyde (1.50 g, 9.62 mmol, 1.00 equiv) in 40 mL THF is added NaOAc (0.79 g, 9.62 mmol, 1.00 equiv), Me₂NH-HCl (863 mg, 10.6 mmol, 1.10 equiv), and AcOH (0.11 mL, 1.9 mmol, 0.20 equiv) at 23 ⁰C. NaBH(OAc)₃ (4.08 g, 19.3 mmol, 2.00 equiv) is added in three portions over five minutes. The suspension is stirred for 12 hours before solvent is removed in vacuo. To the residue is added 10 mL sat. NaHCO_3(aq) and 10 mL CH₂Cl₂. The phases are separated and the aqueous phase is extracted with CH₂Cl₂ (3 x 10 mL). The combined organic phase is concentrated in vacuo. The residue is purified by chromatography on silica gel eluting with hexanes/EtOAc 3:2 (v/v) to afford 1.64 g of the title compound as a colorless liquid (92percent yield). R/= 0.38 (hexane/EtOAc 2:3 (v/v)). NMR Spectroscopy: ¹H NMR (600 MHz, CDCl₃,23 ⁰C, δ): 8.27 (d, J = 8.5 Hz, IH), 7.85 (d, J= 8.2 Hz, IH), 7.79 (dd, J= 6.7 Hz, 2.9 Hz, IH), 7.53 (ddd, J = 8.0 Hz, 6.5 Hz, 1.0 Hz, IH), 7.48 (ddd, J= 6.5 Hz, 5.5 Hz, 1.0 Hz, IH), 7.43- 7.40 (m, 2H), 3.82 (s, 2H), 2.31 (s, 6H). ¹³C NMR (125 MHz, CDCl₃, 23 ⁰C, δ): 134.85, 133.84, 132.52, 128.40, 127.95, 127.38, 125.98, 125.56, 125.06, 124.49, 62.60, 45.69. Mass <n="81"/>Spectrometry: HRMS-FIA (m/z): calcd for [Ci₃Hi₅N + H], 186.1277. Found, 186.1286. These spectroscopic data correspond to reported data (Gay, R.L.; Hauser, CR. J. Am. Chem. Soc. 1967, 89, 2297-2303; incorporated herein by reference).

References: [1] Patent: WO2009/149347, 2009, A1, . Location in patent: Page/Page column 79-80.

3
[ 67-56-1 ]
[ 86-53-3 ]
[ 16413-71-1 ]

References: [1] ACS Catalysis, 2018, vol. 8, # 4, p. 2890 - 2896.

4
[ 50-00-0 ]
[ 14489-75-9 ]
[ 16413-71-1 ]

References: [1] Tetrahedron Letters, 1984, vol. 25, # 24, p. 2535 - 2536.

5
[ 13098-88-9 ]
[ 100-46-9 ]
[ 6343-54-0 ]
[ 16413-71-1 ]

References: [1] Tetrahedron Letters, 1997, vol. 38, # 1, p. 77 - 80.

6
[ 66-77-3 ]
[ 124-40-3 ]
[ 16413-71-1 ]

References: [1] Patent: WO2009/100014, 2009, A1, . Location in patent: Page/Page column 206.

7
[ 3815-24-5 ]
[ 16413-71-1 ]

References: [1] Angewandte Chemie - International Edition, 2019, vol. 58, # 15, p. 4992 - 4997[2] Angew. Chem., 2019, vol. 131, p. 5046 - 5051,6.

8
[ 110-91-8 ]
[ 35480-23-0 ]
[ 2018-89-5 ]
[ 16413-71-1 ]

References: [1] Tetrahedron Letters, 1997, vol. 38, # 1, p. 77 - 80.

9
[ 124-40-3 ]
[ 86-52-2 ]
[ 16413-71-1 ]

References: [1] Tetrahedron Letters, 1999, vol. 40, # 45, p. 7883 - 7887.
[2] Journal of the American Chemical Society, 1967, vol. 89, p. 2297 - 2303.
[3] Journal of the American Chemical Society, 1988, vol. 110, # 19, p. 6579 - 6581.

10
[ 67-56-1 ]
[ 55210-79-2 ]
[ 16413-71-1 ]

References: [1] Green Chemistry, 2018, vol. 20, # 14, p. 3339 - 3345.

11
[ 30354-18-8 ]
[ 972-09-8 ]
[ 16413-71-1 ]

References: [1] Tetrahedron Letters, 1986, vol. 27, # 41, p. 5011 - 5014.
[2] Tetrahedron, 1989, vol. 45, # 4, p. 1155 - 1166.

12
[ 96863-54-6 ]
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[ 96863-61-5 ]