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Chemical Structure| 39895-56-2

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Product Details of [ 39895-56-2 ]

CAS No. :39895-56-2
Formula : C8H11NO
M.W : 137.18
SMILES Code : NCC1=CC=C(CO)C=C1
MDL No. :MFCD06213766
Boiling Point : No data available
InChI Key :WMOUKOAUAFESMR-UHFFFAOYSA-N
Pubchem ID :6496943

Safety of [ 39895-56-2 ]

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

Computational Chemistry of [ 39895-56-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 40.24
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

46.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.53
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.21
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.33
Log Po/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.

0.94
Log Po/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

1.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.86

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.13
Solubility 10.1 mg/ml ; 0.0733 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.

-0.74
Solubility 24.9 mg/ml ; 0.182 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

-2.24
Solubility 0.784 mg/ml ; 0.00571 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

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

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.99 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

1.0
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 [ 39895-56-2 ]

* 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 [ 39895-56-2 ]

[ 39895-56-2 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 24424-99-5 ]
  • [ 39895-56-2 ]
  • [ 123986-64-1 ]
YieldReaction ConditionsOperation in experiment
99% In dichloromethane; at 20℃; for 48h; Boc2O was added in one portion at r.t. to a solution of (4-aminomethyl-phenyl)-methanol Compound 3a (21.2 mmol, 2.9 g) in CH2C12 (100 mL). The resulting solution wasstirred for 48h, then washed with a 10percent citric acid solution (50 mL) followed by brine. Theorganic layer was separated, then dried over Na2SC>4 and filtered. The solvent was removed invacua to obtain (4-hydroxymethyl-benzyl)-carbamic acid tert-butyl ester Compound 3b as awhite solid (5.2 g, 99percent yield), which was used in the next step without further purification.MnO2 (9.6 g) was added to a solution of Compound 3b (21.2 mmol, 5.2 g) inchloroform (60 mL), forming a black suspension that was stirred at r.t. overnight then filteredthrough a pad of celite. The solvent was evaporated in vacua to obtain (4-forinyl-benzyl)-carbamic acid tert-butyl ester Compound 3c as a white solid (4.3 g, 87percent yield), which was usedin the next step without purification.; NaB(OAc)3H (2.8 mmol, 0.58 g) was added to a mixture of Compound 3c (2.6 mmol,0.6 g) and tetrahydro-pyran-4-ylamine Compound 3d (2.6 mmol, 0.26 g) in CH2C12 (25 mL)and the resulting suspension was stirred at r.t. An aliquot of the reaction mixture showed theformation of product (MS m/e 321; 100percent). An aqueous solution of formaldehyde (37percentsolution, 8.6 mmol, 0.7 mL) was added to the reaction mixture, followed by NaB(OAc)3H (2.8mmol, 0.58 g) added in one portion under ice cooling. The reaction mixture was stirred at r.t.for about 2h, then made basic with a 2N NaOH solution and extracted with CH2C12. Theorganic layer was washed with brine, then separated and dried over Na2SO4. The drying agentwas filtered and the solvent was removed in vacua to yield (4-[methyl-(tetrahydro-pyran-4-yl)-amino]-methyl}-benzyl)-carbamic acid tert-butyl ester Compound 3e as a pale yellow oil.MS m/e 235 (M+H, 100percent). The product was purified by column chromatography (4:1CH2Cl2:MeOH) to yield a colorless oil (0.52 g, 59percent yield).; Compound 3e was dissolved in CH2Cl2, then HC1 in dioxane was added and themixture was stirred at r.t. for 12 hrs. The solvent was removed and the gummy residue wasmade basic with 2N NaOH and extracted with EtOAc. The organic layer was washed withbrine, then separated and dried over Na2SO4. The drying agent was filtered and the solvent wasremoved in vacua to obtain (4-aminomethyl-benzyl)-methyl-(tetrahydro-pyran-4-yl)-amineCompound 3f as a pale yellow oil (0.3 g, 83percent yield). MS m/e 235 (M+H, 100percent).; A solution of 3-(3-trifluoromethyl-phenyl)-acryloyl chloride Compound 3g (0.3 mrnol,0.07 g) in THF (2 mL) was added dropwise to a solution of Compound 3f (0.2 mmol, 0.05 g)and Et3N (0.8 mmol, 0.14 mL) in THF (10 mL) at 0°C. The resulting suspension was allowedto warm to r.t. overnight. The reaction mixture was made basic with a 2N NaOH solution andextracted with EtOAc (25 mL). The aqueous layer was extracted with EtOAc (2X10 mL) andthe organic layers were washed with brine, then dried over Na2SO4 and filtered. The solventwas removed in vacua to yield a yellow solid (with methane) as the product. The crude productwas purified by preparative TLC (9:1 EtOAc-.MeOH, Rf = 0.2) to yield N-(4-[methyl-(tetrahydro-pyran-4-yi)-amino]-methyl}-benzyi)-3-(3-trifluoromethyl-phenyl)-acrylamideCompound 3h (0.06 g, 49percent yield). MS m/e 433 (M+H, 100percent).; Mel (0.08 mL, 1.28 mmol) was added dropwise to a solution of Compound 3h (0.07mmol, 0.03 g) in a mixture of acetone:acetonitrile (2 mL). The resulting solution was stirred atr.t. for 24h to provide a residue. The residue was washed with ether (2x 1 mL) and dried undera high vacuum to provide Compound 64 (0.04 g, 93percent yield) as an iodide salt. MS m/e 584(M+H, 100percent).
99% In dichloromethane; at 20℃; for 48h; Boc2O was added in one portion at r.t. to a solution of (4-aminomethyl-phenyl)-methanol Compound 3a (21.2 mmol, 2.9 g) in CH2Cl2 (100 mL). The resulting solution was stirred for 48 h, then washed with a 10percent citric acid solution (50 mL) followed by brine. The organic-layer was separated, then dried over Na2SO4 and filtered. The solvent was removed in vacuo to obtain (4-hydroxymethyl-benzyl)-carbamic acid tert-butyl ester Compound 3b as a white solid (5.2 g, 99percent yield), which was used in the next step without further purification.
88% In chloroform;Inert atmosphere; 1.7 l-'Butoxycarbonylaminomethyl-4-hydroxymethyl benzene, 7.7Amine 6 (1.44g, 10.5 mmol) was dissolved in CHCI3 (50 ml) and Boc20 (2.29 g, 10.5 mmol, 1 eq) was added slowly. The reaction was stirred under nitrogen overnight before the solvent was evaporated and the residue obtained was dissolved in ethyl acetate (50 ml). This solution was washed with a citric acid solution (3 * 50 ml), brine (50 ml), dried over Na2S04, and evaporated to yield 7 as a white solid (2.20 g, 9.2 mmol, 88 percent). Rf = 0.57 (DCM / MeOH sat. N3/4, 8:2); Vmax = cm-1; 'H NMR (300 MHz, CDC13) delta - 7.33 (d, 3J(H,H) = 8.2 Hz, 2H, ArCH a to CH2OH), 7.26 (d, J(H,H) = 8.2 Hz, 2H, ArCH a to CH2NHBoc), 4.86 (bs, 1H, NHBoc), 4.68 (s, 2Eta, CH^OH), 4.30 (d, 3J(H,H) = 5.7 Hz, 2H, CH?NHBoc), 1.96 (bs, 1H, OH), 1.46 (s, 9Eta, C(CH?)3); l 3C NMR (75 MHz, CDC13) delta = 155.9 (CO), 140.0 (ArCCH2OH), 138.3 (ArCCH2NHBoc), 127.6 (ArCH a to CH2NHBoc), 127.2 (ArCH a to CH2OH), 85.2 (C(CH3)3), 65.0 (C3/4OH), 44.4 (CH2NHBoc), 28.4 (C(C3/4)3); HRMS (ESI+): m/z calculated for C,3Hi9N03Na [M + Na]+ : 260.1257, found 260.1253.
31% In dichloromethane; at 20℃; The mixture of (4-(aminomethyl)phenyl)methanol (1 g, 7.29 mmol) and di-tert-butyl dicarbonate (1.59 g, 7.29 mmol) in dichloromethane (30 mL) was stirred at room temperature overnight then concentrated under reduced pressure and the crude product was added to a silica gel column and was eluted with dichloromethane:ethyl acetate (1:1) to give tert-butyl 4-(hydroxymethyl)benzylcarbamate (0.8 g, 2.28 mmol, 31percent yield) as a white solid.1H NMR (400 MHz, DMSO-d6) delta ppm 7.37 (s, 1H), 7.22 (dd, J = 27.8, 8.0 Hz, 4H), 5.13 (t, J = 5.7 Hz, 1H), 4.46 (d, J = 5.7 Hz, 2H), 4.10 (d, J = 6.1 Hz, 2H), 1.36 (s, 9H).

  • 2
  • [ 39895-56-2 ]
  • [ 407-25-0 ]
  • [ 171723-95-8 ]
YieldReaction ConditionsOperation in experiment
15.87 g With triethylamine; In dichloromethane; at 0 - 20℃; for 22.0h; 20.0 g (0328) (132 mmol) of 4-(aminomethyl)benzoic acid was dispersed in 100 mL of anhydrous THF, and 350 mL (2.65 equiv.) of 1M borane-THF in THF was added dropwise. The reaction mixture was heated to reflux for eight hours, and then allowed to cool to room temperature. 100 mL of MeOH was added to quench the remaining borane-THF, and the reaction was stirred for an additional 15 minutes. The reaction solution was then filtered over celite and evaporated in vacuo to give a light yellow solid. 250 mL of DCM was then added to the reaction flask containing the crude intermediate product, followed by 37 mL (2 equiv.) of triethylamine. The reaction was cooled to 0C, 21 mL (1.1 equiv.) of trifluoroacetic anhydride was added dropwise and the reaction was allowed to stir overnight, allowing it to gradually reach room temperature. After 22 hours of reaction time, all of the starting material had been consumed as evidenced by TLC. 250 mL of water was added to the reaction and the organic layer was separated. The aqueous layer was extracted once more with 250 mL of DCM, the combined organics were washed with water (100 mL), and were dried over sodium sulfate, filtered and evaporated in vacuo to give a thick yellow oil. This oil was purified via automated flash chromatography (EPCLC W-Prep 2XY, Yamazen Corp., Yodogawa-Ku Osaka, Japan) using DCM/MeOH as the eluents. The fractions containing the desired product were combined and evaporated to give 15.87 g (51.44% yield for both steps) of 3 as a white solid. lH NMR (300 MHz, CDC13) δ 7.34 (d, J = 8.17 Hz, 2H), 7.26 (d, J = 8.16 Hz, 2H), 6.86 (s, br, 1H), 4.66 (s, 2H), 4.49 (d, J = 5.86 Hz, 2H), 2.02 (s, 1H).
  • 4
  • [ 383-63-1 ]
  • [ 39895-56-2 ]
  • [ 171723-95-8 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine; In methanol; at 25℃; for 2.0h;Inert atmosphere; A solution of 2.55 g of 4-(aminomethyl)benzyl alcohol (18.6 mmol) and 2.64 mL of triethylamine (18.68 mmol) was dissolved in 25 mL of anhydrous methanol, 2.94 mL of ethyl trifluoroacetate (24.6 mmol) was added dropwise under argon atmosphere, and 25 C stirring reaction 2 hours, after the end of the reaction, adding 35mL ethyl acetate and 35mL water extraction,The ethyl acetate layer was washed with saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate overnight. The solvent was removed in vacuo to give crude 4-[(trifluoroacetamido)methyl]benzyl alcohol. The crude product was purified by silica gel column chromatography the eluent was eluted with ethyl acetate / cyclohexane (1: 2, v / v). To give 4-[(trifluoroacetamido)methyl]benzyl alcohol (3.9 g, 20.6 mmol) in 90% yield.
76% With triethylamine; In dichloromethane; at 20℃; for 4.0h;Inert atmosphere; 4-aminomethylbenzyl alcohol (500 mg, 2.89 mmol) was dissolved in 3 ml DCM.TEA (3.0 eq, 1.169 ml, 8.4 mmol) was added dropwise and kept under argon atmosphere. Afterwards, 400 µl (1.2 eq, 3.36 mmol) of EtTFA were added dropwiseand the mixture was stirred in argon atmosphere at room temperature for 4 hr.The reaction was followed up by TLC (DCM:MeOH 5%). The reaction mixture dissolvedin DCM and was washed with brine and the organic phase dried with MgSO4.The organic phase was filtered and evaporated. The crude of the reaction was purified by chromatography (silica gel), eluted with a gradient of 0-5% MeOH inDCM. Yield (1, 500 mg, 76%, white solid).
  • 5
  • [ 24424-99-5 ]
  • [ 39895-56-2 ]
  • [ 156866-52-3 ]
  • 6
  • [ 39895-56-2 ]
  • [ 123986-64-1 ]
 

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