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Chemical Structure| 95-00-1 Chemical Structure| 95-00-1

Structure of 95-00-1

Chemical Structure| 95-00-1

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Product Details of [ 95-00-1 ]

CAS No. :95-00-1
Formula : C7H7Cl2N
M.W : 176.04
SMILES Code : NCC1=C(Cl)C=C(Cl)C=C1
MDL No. :MFCD00008109
InChI Key :SJUKJZSTBBSGHF-UHFFFAOYSA-N
Pubchem ID :1485

Safety of [ 95-00-1 ]

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

Computational Chemistry of [ 95-00-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 44.14
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.05
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

2.29
Log Po/w (WLOGP)?

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

2.3
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.

2.72
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

2.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.42

Water Solubility

Log S (ESOL):?

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

-2.75
Solubility 0.311 mg/ml ; 0.00177 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.

-2.47
Solubility 0.591 mg/ml ; 0.00336 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

-3.67
Solubility 0.0375 mg/ml ; 0.000213 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.

-5.75 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)

1.21

Application In Synthesis of [ 95-00-1 ]

* 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.

  • Downstream synthetic route of [ 95-00-1 ]

[ 95-00-1 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1004-38-2 ]
  • [ 50-00-0 ]
  • [ 95-00-1 ]
  • [ 79988-61-7 ]
  • 2
  • [ 95-00-1 ]
  • [ 364793-57-7 ]
  • 7-bromo-4-(2,4-dichloro-benzylamino)-quinoline-3-carbonitrile [ No CAS ]
  • 3
  • [ 313535-84-1 ]
  • [ 95-00-1 ]
  • 3-(2,4-Dichlorobenzyl)-7-(methoxycarbonyl)-4(3H)-quinazolinone [ No CAS ]
YieldReaction ConditionsOperation in experiment
at 100℃; for 0.0833333h; To 2.70 g of the oil, 2,4-dichlorobenzylamine (3.52 g) was added and the mixture was heated for at 100 C. for 5 min.. After cooling, the residue was washed with water (50 ml) and 2-propanol (50 ml) and dried to give the objective compound (3.10 g) as white crystals. 1H-NMR(DMSO-d6, delta ppm): 3.99(3H, s), 5.26(2H, s), 7.24-7.27(2H, m), 7.42 (1H, d, J=8.4 Hz), 7.44(1H, d, J=2.2 Hz), 8.12(1H, dd, J=8. 3 and 1.7 Hz), 8.25(1H, s), 8.35(1H, d, 8.4 Hz), 8.39(1H, d, 1.4 Hz)
  • 4
  • [ 845894-03-3 ]
  • [ 95-00-1 ]
  • [ 885102-31-8 ]
YieldReaction ConditionsOperation in experiment
Add sodium triacetoxyborohydride (156 mg, 0.73 mmol) to a mixture of 3-fluoro- 4-oxopyrrolidine-l-carboxylic acid tert-butyl ester (100 mg, 0.5 mmol) and 2,4- dichlorobenzylamine (65 muL, 0.5 mmol) in 1,2-dichloroethane (1.5 mL), followed by 2 drops of glacial acetic acid and stir overnight at room temperature. Pour the crude mixture into 2 N sodium hydroxide and extract with ethyl acetate, wash with water, dry (magnesium sulfate), concentrate and chromatograph on silica gel to give 3 -(2,4- dichlorobenzylamino)-4-fluoropyrrolidine-l-carboxylic acid tert-butyl ester (40 mg, 20%). 1H NMR (300 MHz, CDCl3) delta 7.36-7.44 (2H, m), 7.20-7.28 (IH, m), 5.03 (IH, d, J = 54.07 Hz)5 3.21-3.95 (6H, m), 2.99-3.15 (IH, m), 1.45 (9H5 s), MS (ES): m/z = 363 [M+].
  • 5
  • [ 32618-85-2 ]
  • [ 95-00-1 ]
  • [ 939979-13-2 ]
YieldReaction ConditionsOperation in experiment
(2) Phosphorous oxychloride(41.45 g) was added to 6-nitro-1H-quinazolin-2,4-dione(3.0 g) and the mixture was stirred under reflux overnight. The reaction solution was concentrated, toluene was added to the residue and it was concentrated again. Chloroform was added to the residue, the precipitate was filtered, and water was added to the filtrate and it was separated. The organic layer was dried and the solvent was concentrated. Acetonitrile(50 mL) was added to the residue and the mixture was cooled to 0C, a solution of 2,4-dichlorobenzylamine(1.06 g) in acetonitrile(20 mL) was added dropwise. After stirring at 0C for 15 minutes, chloroform and water was added to the reaction solution. The organic layer was separated , dried and the solvent was concentrated. Diisopropyl ether was added to the residue, the precipitate was filtered and dried to give (2-chloro-6-nitro-quinazolin-4-yl)-(2,4-dichlorobenzyl)-amine(832 mg) as a yellow powder. APCI-MS(m/e):383/385[M+H]+.
  • 6
  • [ 149057-19-2 ]
  • [ 95-00-1 ]
  • [ 1311150-51-2 ]
  • 7
  • [ 1184-90-3 ]
  • [ 95-00-1 ]
  • [ 1415910-65-4 ]
  • 8
  • [ 4565-31-5 ]
  • [ 95-00-1 ]
  • 5-formyl-thiophene-2-carboxylic acid 2,4-dichlorobenzylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% To a suspension of 5-Formyl- 2- thiophenecarboxylic acid (2 g, 12.81 mmol) in 50 ml dichloromethane at 0°C, 1-Chlor-N,N,2-trimethylpropinylamin (1.88 g, 14.1 mmol) was added. The mixture was stirred 5 min at 0°C and then was allowed to reach RT and stirred at this temperature for 15 min. To the obtained clear solution, a solution of 2,4-dichlorobenzylamine (2.5 g, 14.1 mmol) and triethylamine (19.2 mmol) in 10 ml dichloromethane were added and the reaction was stirred at RT overnight. The mixture was diluted with dichloromethane and washed with aqueous HCl (0.25 M). The organic layer was dried, filtered off and concentrated under reduced pressure. The obtained residue- 5-Formyl-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide (Intermediate 7)- (3.3g, 82percent) was used in the next step without further purification. 1 H NMR (DMSO-d6, 500 MHz) delta ppm 9.9 (s, 1 H), 9.41 (t, 1 H), 8.07 (d, 1 H), 7.98 (d, 1 H), 7.53 (s, 1 H), 7.49-7.35 (m, 2H), 4.52 (d, 2H). LC/MS (Method 2) Rt = 1.73 min; detected mass: m/z = 360.12 ([M+H]+).
82% Intermediate 7: <strong>[4565-31-5]5-formyl-thiophene-2-carboxylic acid</strong> 2,4-dichlorobenzylamide To a suspension of 5-Formyl- 2- thiophenecarboxylic acid (2 g, 12.81 mmol) in 50 ml dichloromethane at 0°C, 1 -Chlor-N,N,2-trimethylpropinylamin (1 .88 g, 14.1 mmol) was added. The mixture was stirred 5 min at 0°C and then was allowed to reach RT and stirred at this temperature for 15 min. To the obtained clear solution, a solution of 2,4- dichlorobenzylamine (2.5 g, 14.1 mmol) and triethylamine (19.2 mmol) in 10 ml dichloromethane were added and the reaction was stirred at RT overnight. The mixture was diluted with dichloromethane and washed with aqueous HCI (0.25 M). The organic layer was dried, filtered off and concentrated under reduced pressure. The obtained residue- 5-Formyl-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide (Intermediate 7)- (3.3g, 82percent) was used in the next step without further purification. 1 H NMR (DMSO-d6, 500 MHz) delta ppm 9.9 (s, 1 H), 9.41 (t, 1 H), 8.07 (d, 1 H), 7.98 (d, 1 H), 7.53 (s, 1 H), 7.49-7.35 (m, 2H), 4.52 (d, 2H). LC/MS ( Method 2) Rt = 1 .73 min;detected mass: m/z = 360.12 ([M+H]+).
  • 9
  • [ 4565-31-5 ]
  • [ 95-00-1 ]
  • 5-[4-(2,6-dimethyl-pyridin-4-yl)-piperazin-1-ylmethyl]-thiophene-2-carboxylic acid 2,4-dichloro-benzylamide [ No CAS ]
  • 10
  • [ 97-08-5 ]
  • [ 95-00-1 ]
  • 4-chloro-3-nitro-N-2,4-dichlorobenzylbenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; at 20℃; General procedure: <strong>[97-08-5]4-Chloro-3-nitrobenzenesulfonyl chloride</strong> (1 equiv.) anddifferent amines (2 equiv.) were added to a 50 mL roundbottomedflask and dissolved in acetonitrile (25 mL). Thecontents were then stirred for 1-2 h at room temperature.Afterward, the solvent was removed under vacuum andthe product was washed with a dilute solution (5 %) ofNaHCO3 and filtered.
  • 11
  • [ 34622-39-4 ]
  • [ 95-00-1 ]
  • (S)-N-(2,4-dichlorobenzyl)-6-oxopiperidine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 24h; A mixture of <strong>[34622-39-4](S)-6-oxopiperidine-2-carboxylic acid</strong> (1.00 g, 6.99 mmol), 2,4-dichlorobenzylamine (1.48 g, 8.38 mmol) and 3-[(ethylimino)methylene]amino}-N,N-dimethylpropan-1-aminiumchloride (EDCI) (1.61 g, 8.38 mmol), in CH2Cl2 was stirred at r.t. for 24 h. Solvents were evaporated and the mixture was solved in EtOH (40 mL), then Et2O was added (60 mL). The desired product crystalized over night. It was filtered to give a white solid in 62percent yield (1.30 g, 4.32 mmol). mp (EtOH/Et2O) 142-144 °C; TLC Rf (CH2Cl2/MeOH: 96/4) 0.3; 1H NMR (DMSO[d6], 400 MHz): delta ppm 1.56-1.81(m, 3H, CH2CH2CH2CH), 1.86-1.96 (m, 1H, CH2CH2CH2CH), 2.15 (t, J=6.8 Hz, 2H, CH2CH2CH2CH), 3.95 (dd, J= 5.9, 3.0 Hz, 1H,CH2CH2CH2CH), 4.28 (dd, J = 15.8, 5.6 Hz, 1H, NHCH2), 4.37 (dd, J = 15.8, 5.6 Hz, 1H, NHCH2), 7.38 (d, J = 8.3 Hz, 1H, ArH), 7.42 (dd, J = 8.3, 2.1 Hz, 1H, ArH), 7.57 (br d, J = 2.5 Hz, 1H, NHCH), 7.60 (d,J= 2.1 Hz, 1H, ArH), 8.52 (br t, J = 5.8 Hz, 1H, NHCH2); 13C NMR(DMSO[d6],100 MHz): delta ppm 18.9 (CH2), 26.4 (CH2), 31.7 (CH2), 40.2 (CH2), 55.4 (CH), 127.7 (CH), 128.9 (CH), 130.6 (CH), 132.6 (C), 133.3 (C), 135.9 (C), 170.9 (CH), 172.7 (C). Anal. Calcd for C13H14Cl2N2O2: C, 51.85; H, 4.69; N, 9.30. Found: C, 51.82; H, 4.70; N, 9.29percent.
  • 12
  • [ 34622-39-4 ]
  • [ 95-00-1 ]
  • (2S)-(5E)-N-(2,4-dichlorobenzyl)-5-[(dimethylamino)methylene]-6-oxopiperidine-2-carboxamide [ No CAS ]
  • 13
  • [ 3202-33-3 ]
  • [ 95-00-1 ]
  • [ 13939-06-5 ]
  • N-(2,4-dichlorobenzyl)-4-phenoxypiperidine-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% With copper diacetate; palladium diacetate; 1,8-diazabicyclo[5.4.0]undec-7-ene; In 1,4-dioxane; at 95℃; General procedure: The reaction was performed in a double-chamber system [67,68]. Amine/amines, Pd(OAc)2(0.05 equiv.) and Cu(OAc)2 (0.5 equiv.) were added to the reaction chamber and dissolved in1,4-dioxane (2 mL). In the CO-chamber was Mo(CO)6 (200 mg) dissolved in 1,4-dioxane (2 mL).After capping of the system, 1,8-diazabicyclo[5.4.0]undec-7-ene was added to the CO-chamber.The double-chamber system was positioned in a Dry-Syn heating block and heated to 95 C. Aftercompletion of the reaction, the reaction mixture was filtered through a short silica plug before flashcolumn chromatography.
  • 14
  • [ 3202-33-3 ]
  • [ 10456-04-9 ]
  • [ 95-00-1 ]
  • [carbonyl-11C]N-(2,4-dichlorobenzyl)-4-phenoxypiperidine-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With PdCl2(xantphos); In tetrahydrofuran; at 120℃; for 0.166667h;Sealed tube; General procedure: Pd(Xantphos)Cl2 (4 mol) and amine/amines (30 mol) were added to an oven-dried, conicalglass vial followed by freshly distilled tetrahydrofuran (400 L). [11C]CO was transferred to the cappedreaction vial and the radioactivity was measured to determine the starting amount of [11C]CO. Thereaction was heated at 120 C for 10 min. When finished, the radioactivity was measured to confirm thatno radioactive material had escaped during heating. The vial was purged with N2 to remove unreacted[11C]CO and, possibly, volatile labelled compounds formed during the reaction. The radioactivity wasmeasured after the purge followed by either analytical HPLC for product selectivity determination orsemi-preparative HPLC purification for 11C-labelled product isolation. Purification was performedusing either column C1 = Phenomenex Kinetex C18 (5 m, 150 10.0 mm) column, C2 = Reprosil-PurBasic C18 (5 m, 150 10.0 mm) column or C3 = Gemini NX C18 (5 m, 250 10.0 mm) columnwith ammonium formate buffer 50 mM (pH 3.5) (A) and acetonitrile (B) as eluents. Run time was20 min with flow 5 mL/min followed by flushing the column with 100% B. After isolation and afinal radioactivity measurement of the 11C-labelled product, an aliquot was analysed to determineradiochemical purity and the identity of the 11C-labelled product was confirmed using the isotopicallyunmodified product as reference. The analytical method was the same for all compounds, 10-90%acetonitrile in 10 min (flow 2 mL/min). Molar activity determinations were based on a calibrationcurve, constructed with isotopically unmodified 20. For full definitions and calculations, see thesupporting materials.
 

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Technical Information

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