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Chemical Structure| 10429-82-0

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Product Details of [ 10429-82-0 ]

CAS No. :10429-82-0
Formula : C11H16Cl3N
M.W : 268.61
SMILES Code : ClCCN(CC1=CC=CC=C1)CCCl.[H]Cl
MDL No. :MFCD00185654
InChI Key :AZRWNJFEUSHORT-UHFFFAOYSA-N
Pubchem ID :2777881

Safety of [ 10429-82-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 10429-82-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.45
Num. rotatable bonds 6
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 70.09
TPSA ?

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

3.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

3.74
Log Po/w (WLOGP)?

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

3.62
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.

3.6
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

3.47
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.88

Water Solubility

Log S (ESOL):?

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

-3.76
Solubility 0.0465 mg/ml ; 0.000173 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.

-3.5
Solubility 0.0849 mg/ml ; 0.000316 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

-5.0
Solubility 0.0027 mg/ml ; 0.0000101 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

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

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.

-5.28 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

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)

1.38

Application In Synthesis of [ 10429-82-0 ]

* 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 [ 10429-82-0 ]

[ 10429-82-0 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 10429-82-0 ]
  • [ 99365-48-7 ]
  • [ 1172589-33-1 ]
YieldReaction ConditionsOperation in experiment
85% Step 1: A stirred solution of <strong>[99365-48-7]4-bromoindolin-2-one</strong> (13.0 g, 61.3 mmol) inTHF (500 mL) was treated by the dropwise addition of a l.OM THF solution of NaHMDS (306 mL, 306 mmol) at -780C under nitrogen. After stirring at -78C for 30 minutes, N- benzylbis(2-chloroethyl)amine hydrochloride (18.05 g, 67.4 mmol) was added as a solid. The reaction mixture was stirred at -78C for 30 minutes and then allowed to warm to room temperature. The reaction mixture was then heated to reflux for 12 hours. After cooling to 00C, the reaction was quenched by the addition of saturated aqueous NH4Cl solution. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (3 X 200 mL). The combined organics layers were washed with brine, dried with MgSO4 and concentrated under reduced pressure. The resulting solid was triturated with DCM/EtOAc to give r-benzyl-4-bromospiro[indoline-3,4'-piperidin]-2-one (19.3 g, 85%) as a solid. LCMS (APCI+) m/z 371/373 [M+H]+; Rt = 2.71 min.
General procedure: To a suspension of 5-methoxy-1H-pyffolo[3,2-b]pyridin-2(3H)-one (1.85 g, 11.3 mmol, CAS RN 178393-14-1) in THF (80 mL) at -78C was added dropwise LiHMDS (50.3 mL, 50.3 mmol, 1M solution in THF) and the brown solution was stirred at this temperature over 30 mm. before N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (3 g, 11.2 mmol, CAS RN 10429-82-0) was added in one portion. The cooling bath was then removed and the mixture wasallowed to warm up to RT. Heating was installed and the light brown suspension was stuffed at reflux for 24 hours. The light brown reaction mixture was poured on saturated aqueous NH4C1 solution and EtOAc and the layers were separated. The aqueous layer was twice extracted with EtOAc. The organic layer was dried over Mg504, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 40 g column using an MPLCsystem eluting with a gradient of n-heptane : EtOAc (100: 0 to 0: 100). The product containing fractions were combined. The precipitate formed during evaporation was filtered off to afford the title product as a light brown solid (0.288 g; 8%).
  • 2
  • [ 42303-42-4 ]
  • [ 10429-82-0 ]
  • ethyl 1-( 4-benzylpiperazin-1-yl)cyclopropanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
47.8% With N-ethyl-N,N-diisopropylamine; In ethanol; for 16h;Reflux; A mixture of <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (120 g, 0.725 mol), N,N- diisopropylethylamine (942 g, 7.29 mol), N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (213 g, 0.793 mol) in anhydrous ethanol (1.6 L) was stirred under reflux for 16 h. TLC (PE:EtOAc = 5:1,f= 0.4) showed that most of the starting material was consumed. Then the mixture was concentrated. The residue was partitioned between dichloromethane (1 L) and water (0.5 L). The layers were separated and the aqueous layer was extracted with dichloromethane (0.5 L x 2). The combined organic layers were concentrated. The residue was purified by chromatography on silica gel (PE:EtOAc = 20:1 to 10:1) to give ethyl l-(4-benzylpiperazin-l-yl)cyclopropanecarboxylate (100 g, 47.8%) as a light yellow oil.1H-NMR (400MHz, chloroform-di): delta [ppm] = 0.88-0.97 (m, 2H), 1.23-1.36 (m, 5H), 2.37 (br. S, 4H), 2.98 (br. S, 4H), 3.51 (s, 2H), 4.15 (q, 2H), 7.23-7.36 (m, 5H).
47.8% With N-ethyl-N,N-diisopropylamine; In ethanol; for 16h;Reflux; A mixture of <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (120 g, 0.725 mol), N,N- diisopropylethylamine (942 g, 7.29 mol), N-benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (213 g, 0.793 mol) in anhydrous ethanol (1.6 L) was stirred under reflux for 16 h. TLC (PE:EtOAc = 5:1, Rf = 0.4) showed that most of the starting material was consumed. Then the mixture was concentrated. The residue was partitioned between dichloromethane (1 L) and water (0.5 L). The layers were separated and the aqueous layer was extracted with dichloromethane (0.5 L x 2). The combined organic layers were concentrated. The residue was purified by chromatography on silica gel (PE:EtOAc = 20:1 to 10:1) to give ethyl l-(4-benzylpiperazin-l-yl)cyclopropanecarboxylate (100 g, 47.8%) as a light yellow oil. 1H-NM (400MHz, chloroform-di): delta [ppm] = 0.88-0.97 (m, 2H), 1.23-1.36 (m, 5H), 2.37 (br. S, 4H), 2.98 (br. S, 4H), 3.51 (s, 2H), 4.15 (q, 2H), 7.23-7.36 (m, 5H).
43% With N-ethyl-N,N-diisopropylamine; In ethanol; for 16h;Reflux; A mixture of ethyl 1- aminocyclopropanecarboxylate hydrochloride (2.4 g, 14.5mmol), N-benzyl-2-chloro-N-(2- chloroethyl)ethanamine hydrochloride (4.26 g, 15.8 mmol), and N,N-Diisopropylethylamine (25 mL) in ethanol (32 mL) was stirred at reflux for 16 hours. The reaction mixture was concentrated to dryness. The residue was partitioned between dichloromethane and water. Two layers were separated, and the aqueous layer was extracted with dichloromethane. The combined organic layers were concentrated. The residue was purified by silica gel column (pet. ether/EtOAc = 1 :0-10: 1 ) to give ethyl l-(4-benzylpiperazin-l-yl)cyclopropanecarboxylate (1-61-2, 1.8 g, yield: 43%) as a yellow oil. 1H NMR (400 MHz, CDC13) delta: 7.37-7.27 (m, 5H), 4.19-4.13 (m, 2H), 3.54 (s, 2H), 3.00(brs, 2H), 2.39 (brs, 2H), 1.31-1.26 (m, 5H), 7.52 (m 1H), 0.93-0.91 (m, 2H).
24% With sodium hydrogencarbonate; In ethanol; at 80℃; for 4h; N-Benzyl-2-chloro-N-(2-chloroethyl)ethanamine hydrochloride (obtained in the previous step, 10.37 g, 38.61 mmol) was added to a solution of <strong>[42303-42-4]ethyl <strong>[42303-42-4]1-aminocyclopropanecarboxylate hydrochloride</strong></strong> (6.4 g, 38.6 mmol) and NaHCO3 (17.5 g, 208.5 mmol) in EtCH (200 mL). The reaction mixture was stirred at 80 C for 4 hand overnight at rt. The solvent was concentrated and the crude product was diluted with AcOEt and water. The layers were separated and the organic layer was driedover Na2SO4, filtered and concentrated. The crude residue was purified by flash chromatography on silica gel, eluents CH/AcOEt (100:0 to 0:100) to give the title compound (2.86 g, 24% yield).HPLC-MS (Method A): Ret, 2.26 mm; ESl-MS m/z, 289 (M÷1).

  • 3
  • [ 500912-18-5 ]
  • [ 10429-82-0 ]
  • 1-benzyl-4-(2-fluoro-6-methoxyphenyl)piperidine-4-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
132 mg First, sodium bis(trimethylsilyl) amide (1.0 M tetrahydrofuran solution) (1.6 mL) was added dropwise to a solution of <strong>[500912-18-5]2-<strong>[500912-18-5](2-fluoro-6-methoxyphenyl)acetonitrile</strong></strong> (86 mg) in tetrahydrofuran (2.4 mL) under ice cooling, and the mixture was stirred at the same temperature for 30 minutes. N-benzyl-bis(2-chloroethyl)amine hydrochloride (140 mg) was added to the resultant solution, followed by reflux for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then was dried with anhydrous magnesium sulfate. the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by silica gel column chromatography (diethylether/n-hexane = 50/50) to obtain 1-benzyl-4-(2-fluoro-6-methoxyphenyl)piperidine-4-carbonitr ile (132 mg). 1H-NMR (400MHz, CDCl3) delta: 2.28-2.37(m,2H),2.43-2.50(m,2H),2.50-2.59(m,2H),2.89-2.98(m ,2H),3.58(s,2H),3.91(s,3H),6.67(ddd,J=12.9,8.4,1.2Hz,1H),6. 74(d,J=8.3Hz,1H),7.21-7.29(m,3H),7.29-7.36(m,4H).
 

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