(3-Fluorophenyl)methanamine

Cat.NO.:A114357 Purity:95%

Product Details of [ 100-82-3 ]

CAS No. :	100-82-3
Formula :	C₇H₈FN
M.W :	125.14
SMILES Code :	NCC1=CC(F)=CC=C1
MDL No. :	MFCD00008113
InChI Key :	QVSVMNXRLWSNGS-UHFFFAOYSA-N
Pubchem ID :	66853

Safety of [ 100-82-3 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H314
Precautionary Statements:	P280-P305+P351+P338-P310
Class:	8
UN#:	2735
Packing Group:	Ⅱ

Computational Chemistry of [ 100-82-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.14
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	34.07
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	26.02 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.56
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	1.24
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.55
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.	1.97
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	1.88
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.64

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.82
Solubility	1.87 mg/ml ; 0.015 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.38
Solubility	5.16 mg/ml ; 0.0413 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-2.68
Solubility	0.262 mg/ml ; 0.00209 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	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	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.	-6.18 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 [ 100-82-3 ]

* 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 [ 100-82-3 ]

[ 100-82-3 ] Synthesis Path-Downstream 1~7

1
[ 137640-84-7 ]
[ 100-82-3 ]
C₂₀H₁₄F₄N₂O₂ [ No CAS ]

References: [1]Patent: EP1207154,2002,A1 .Location in patent: Example 75.

2
[ 351003-49-1 ]
[ 100-82-3 ]
[ 1225040-05-0 ]

References: [1]Organic Letters,2010,vol. 12,p. 2182 – 2185.

3
[ 100-82-3 ]
[ 1224944-51-7 ]
[ 1224939-90-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-ethyl-N,N-diisopropylamine; In ethanol; for 4h;Reflux; Inert atmosphere;	A solution of methyl 5-chloropyrazolo[l,5-alpha]pyrimidine-3-carboxylate (240 mg, 1.1 mM, 1.0 equiv), 3-fluorobenzylamine (200 uL, 2.0 mM, 2.0 equiv), 30 mL of ethanol and 400 uL of N,N-diisopropylethylamine (2.0 mM, 2 equiv) were combined and heated under reflux for 4 hours. The mixture was concentrated and the product collected by filtration and washed with cold ethanol to give 271 mg (80%) of methyl 5-(3- fluorobenzylamino)pyrazolo[l,5-alpha]pyrimidine-3-carboxylate LCMS (ESI) m+H = 301.2, 1H NMR (400 MHz, OMSO-d6) delta: 8.56 (d, 1 H), 8.41 (m 1 H), 8.17 (s, 1 H), 7.35 (m, 3 H), 7.08 (td, 1 H), 6.44 (d, 1 H), 4.61 (d, 2 H), 3.74 (s, 3 H).
80%	With N-ethyl-N,N-diisopropylamine; In ethanol; for 4h;Reflux; Inert atmosphere;	A solution of <strong>[1224944-51-7]methyl 5-chloropyrazolo[1,5-c]pyrimidine-3-carboxylate</strong> (240 mg, 1.1 mM, 1.0 equiv), 3-fluorobenzylamine (200 uL, 2.0 mM, 2.0 equiv), 30 mL of ethanol and 400 uL of N,N-diisopropylethylamine (2.0 mM, 2 equiv) were combined and heated under reflux for 4 hours. The mixture was concentrated and the product collected by filtration and washed with cold ethanol to give 271 mg (80%) of methyl 5-(3-fluorobenzylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylate LCMS (ESI) m+H=301.2, 1H NMR (400 MHz, DMSO-d6) delta: 8.56 (d, 1H), 8.41 (m 1H), 8.17 (s, 1H), 7.35 (m, 3H), 7.08 (td, 1H), 6.44 (d, 1H), 4.61 (d, 2H), 3.74 (s, 3H).

References: [1]Patent: WO2010/51549,2010,A1 .Location in patent: Page/Page column 81-82.
[2]Patent: US2012/22043,2012,A1 .Location in patent: Page/Page column 35.

4
[ 100-82-3 ]
[ 23020-15-7 ]
[ 1531592-25-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 288 – 293.

5
[ 100-82-3 ]
[ 369-26-6 ]
[ 598-21-0 ]
methyl 4-fluoro-3-(2-((3-fluorobenzyl)am ino)acetamido)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.02 g		Bromoacetyl bromide (1.1 mL, 12.5 mmol) was added dropwiseto a mixture of the<strong>[369-26-6]methyl 3-amino-4-fluorobenzoate</strong> (i.85g, 10.9 mmol) and diisopropylethylamine (2.8 mL, 16.4mmol) in dichloromethane at 0 °C. After stirring for 30 minutes at 0 °C, the reaction mixture was diluted with dichloromethane and water. The layers were separated and the aqueous phase was washed with dichloromethane (2x). the combined organic layers were dried over MgSO4 and concentrated (aspirator) to give a dark brown liquid. LCMS showed that the amide was themajor component and the aniline was a minor component. The mixture was dissolved in DMF (30 mL) and potassium carbonate (1.7 g, 12.3 mmol) was added. To the mixture was added 3- fluorobenzylamine (1.4 g, 10.9 mmol) and the reaction stirred at room temperature for 16 hours. The reaction was diluted with water (300 mL) and the aqueous solution was extracted with ethyl acetate (3x). The combined organic layers were washed with water, brine, and were dried overMgSO4. The mixture was filtered and concentrated and the crude residue was purified by flash chromatography (silica gel, 0-60percent ethyl acetate/hexanes) to give 2.02 g of 1-53. 1H NMR7.38-7.29 (m, 3H), 7.25 (appdt, J=8.3, 6.0 Hz, 1H), 4.35 (s, 2H), 4.09 (s, 2H), 3.91 (s, 3H). ESIMS m/z335.1 (M+H)+

References: [1]Patent: WO2016/174616,2016,A1 .Location in patent: Page/Page column 49; 50.

6
[ 100-82-3 ]
[ 2815-95-4 ]
3-(benzo[d][1,3]dioxol-5-yl)-N-(3-fluoro-benzyl)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%		General procedure: A solution of 1,3-benzodioxole-5-propanoic acid (20mmol) in anhydrous DMF (30ml) was treated with PyBOP (22mmol) followed by DIEPA (60mmol). After stirring at room temperature for 20 min, the corresponding amine (20mmol) was added, and the solution was stirred at room temperature overnight. The reaction was diluted with dichloromethane (100 ml) and water (100 ml). The layers were separated and the organic layer was washed with water (3 x 25 ml). The combined aqueous washes were then back-extracted with dichloromethane (50 ml), The combined organic layers were washed with brine (50 ml) and dried over magnesium sulfate, filtered and finally evaporated in vacuo. The crude material was purified by column chromatography over silica gel(dichloromethane/methanol: 100/0 to 92/8) to give the title compound (2a-2f).

References: [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4571 – 4575.

7
[ 100-82-3 ]
[ 455-37-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With tert.-butylhydroperoxide; caesium carbonate; In water; acetonitrile; for 4h;Reflux;	General procedure: To a solution of 4-methoxybenzyl amine (1.0 mmol) and cesium carbonate (1.0 mmol) in 3 mL of CH3CN was added a solution of 70% aqueous TBHP (3.0 mmol) and the mixture was refluxed for 4 h. The mixture was then dried to vacuum and extracted three times with ethyl acetate followed by washing with brine,and dried over anhydrous Na2SO4. Evaporation of the solvent under vacuum afforded the crude product, which was furthur purified by column chromatography using hexane/ethyl acetate mixture and then analyzed by spectroscopy.

References: [1]Dalton Transactions,2020,vol. 49,p. 3480 – 3487.
[2]Tetrahedron Letters,2019,vol. 60.

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