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Chemical Structure| 39178-35-3 Chemical Structure| 39178-35-3

Structure of 39178-35-3

Chemical Structure| 39178-35-3

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Product Details of [ 39178-35-3 ]

CAS No. :39178-35-3
Formula : C6H5Cl2NO
M.W : 178.02
SMILES Code : O=C(Cl)C1=CC=NC=C1.[H]Cl
MDL No. :MFCD00012830
InChI Key :BNTRVUUJBGBGLZ-UHFFFAOYSA-N
Pubchem ID :12262826

Safety of [ 39178-35-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H312-H314-H332
Precautionary Statements:P260-P261-P264-P270-P271-P280-P301+P312-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P312-P321-P322-P330-P363-P405-P501
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 39178-35-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 41.39
TPSA ?

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

29.96 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

2.1
Log Po/w (WLOGP)?

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

2.26
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.

0.73
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

1.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.39

Water Solubility

Log S (ESOL):?

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

-2.64
Solubility 0.403 mg/ml ; 0.00227 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.

-2.36
Solubility 0.778 mg/ml ; 0.00437 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

-2.56
Solubility 0.487 mg/ml ; 0.00274 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

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

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.

-5.89 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)

1.15

Application In Synthesis of [ 39178-35-3 ]

* 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 [ 39178-35-3 ]

[ 39178-35-3 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 39178-35-3 ]
  • [ 456-00-8 ]
  • [ 113485-27-1 ]
  • 2
  • [ 39178-35-3 ]
  • [ 62-53-3 ]
  • [ 3034-31-9 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In 1,2-dichloro-ethane; at 0 - 20℃; for 2.41667h;Heating / reflux; To a slurry comprising 500 ml of a 1,2-dichloroethane solutioncontaining 50 g of isonicotinic acid chloride hydrochloride andcooled to 0C were gradually added dropwise 31.4 g of aniline and50 ml of a 1,2-dichloroethane solution containing 60 g oftriethylamine over 25 minutes or longer. After stirring themixture at room temperature for 30 minutes, it was stirred underreflux for 1.5 hours. To the reaction mixture was added 100 ml ofwater and the mixture was gradually cooled to 0C. The formedprecipitates were collected by filtration, dried under reducedpressure, washed with diethyl ether, and dried under reduced 'pressure to give 45 g of N-phenylisonicotinic amide shown in Table55 below.
  • 3
  • [ 7210-76-6 ]
  • [ 39178-35-3 ]
  • ethyl 2-(isonicotinamido)-4-methylthiazole-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine; In tetrahydrofuran; at 20℃; for 48h; Synthesis of Ethyl 2-(lsonicotinamido)-4-methylthiazole~5~carboxylateTo a mixture of ethyl 2-amino-4-methylthiazole-5-carboxylate (5.70 g, 30.60 <n="93"/>mmol) and triethylamine (10.0 ml_, 71.80 mmol) in tetrahydrofuran (100 ml_) was added isonicotinoyl chloride hydrochloride (6.00 g, 32.00 mmol). The reaction mixture was stirred at ambient temperature for 2 days. The solvent was removed by evaporation and the resulting white solid was washed sequentially with water, 10% sodium bicarbonate solution, and water, then dried to afford the title compound in 90% yield (8.10 g); 1H NMR (DMSO-d6, 300 MHz) δ 8.77 (d, J = 6.0 Hz, 2H), 8.77 (d, J = 6.0 Hz, 2H), 4.23 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H). 1.27 (t, J = 7.2 Hz, 3H); MS (ES+) m/z 292.0 (M + 1).
  • 5
  • [ 1496-40-8 ]
  • [ 39178-35-3 ]
  • [ 218156-96-8 ]
YieldReaction ConditionsOperation in experiment
86.3% With triethylamine; In dichloromethane; at 0℃; for 0.5h;Product distribution / selectivity; Isonicotinoyl chloride hydrochloride (6.48 g, 36.4 mmol, commercially available product) and triethylamine (5.57 ml, 54.6 mmol) were sequentially added at 0C to a dichloromethane (10 ml) solution of <strong>[1496-40-8]2-(1-piperidinyl)-5-(trifluoromethyl)aniline</strong> (4.45 g, 18.2 mmol) obtained as described in Referential Example 1-2B. The mixture was stirred for half an hour. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate = 1/1) and recrystallization. Thus, N-[2-(1-piperidinyl)-5-(trifluoromethyl) phenyl]isonicotinamide (SRPIN-1, GIF-0340) (5.49 g, 86.3%) was yielded as a colorless solid.
75% With triethylamine; In dichloromethane; at 0 - 20℃; for 3h; A 25 mL round bottom flask initiallyplaced in an ice bath was charged with 0.629 g (3.389 mmol) ofisonicotinoyl chloride hydrochloride, 0.800 mL of triethylamine,8.00 mL of dichoromethane and 0.400 (1.64 mmol) of 2-(piperidin-1-yl)-5-(trifluoromethyl) aniline (8). The ice-bathwas removed andthe mixture was magnetically stirred at room temperature for 3 h.Then, 10.0 mL of distilled water was added, and the mixture wastransferred to a separatory funnel. The aqueous layer was extractedwith ethyl acetate (4 x 30.0 mL). The organic extracts were combinedand the resulting organic layer was washed with brine, driedover sodium sulphate, filtered, and concentrated under reducedpressure. The residue was purified by silica gel column chromatographyeluted with hexane-ethyl acetate (3:1 v/v). The solid wasfurther recrystallized with acetone. The compound SRPIN340 wasobtained as a white solid in 75% yield (430 mg, 1.23 mmol).TLC Rf = 0.13 (hexane - ethyl acetate 3:1 v/v). mp 95.6-96.7 C.IR (ATR, cm-1) numax: 3347, 2945, 2917, 2811, 1679, 1611, 1587, 1556,1527, 1455, 1434, 1380, 1334, 1308, 1239, 1165, 1107, 1093, 1061,1022, 915, 895, 878, 839, 826, 751, 728, 681, 662, 644. 1H NMR(300 MHz, CDCl3) delta: 1.65-1.81 (m, 6H), 2.86 (t, 4H, J = 5.1 Hz), 7.28(d, 1H, J = 8.4 Hz), 7.37 (dd, 1H, J = 8.4 Hz and J = 1.8 Hz), 7.76 (dd,2H, J = 4.5 Hz and J = 1.5 Hz), 8.83-8.85 (m, 3H), 9.55 (s, 1H, NH).13C NMR (75 MHz, CDCl3) delta: 24.0, 27.1, 53.8, 116.6, 120.8, 121.1, 121.6(q, J C-F =3.7 Hz), 124.2 (q, J C-F = 270.5 Hz), 127.5 (q, J C-F = 32.3 Hz),133.4, 141.8, 145.9, 151.1, 163.0. HRMS (M + H+): Calculated forC18H19F3N3O, 350.1480; found: 350.1420.
33.9% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 19.5h;Product distribution / selectivity; Isonicotinoyl chloride hydrochloride (151 mg, 0.850 mmol, commercially available product), triethylamine (450 mul, 3.23 mmol), and a catalytic amount of 4-(dimethylamino)pyridine were sequentially added at 0C to a dichloromethane (5 ml) solution of <strong>[1496-40-8]2-(1-piperidinyl)-5-(trifluoromethyl)aniline</strong> (173 mg, 0.708 mmol), obtained as described in Referential Example 1-2A. The resulting mixture was warmed to room temperature and stirred for 19.5 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium bicarbonate, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (10 g, hexane/ethyl acetate = 1.5/1) and recrystallization (hexane). Thus, N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinamide (SRPIN-1, code name GIF-0340) (83.8 mg, 0.240 mmol, 33.9%) was yielded as a colorless solid. The melting point, and results of TLC and 1H NMR (CDCl3, 400 MHz), are as follows: m.p. 96-98C; TLC Rf 0.40 (hexane/ethyl acetate = 1/1); 1H NMR (CDCl3, 400 MHz) delta 1.67-1.68 (m, 2H, CH2), 1.78 (tt, 4H, J = 5.5, 5.5 Hz, 2CH2), 2.88 (t, 4H, J = 5.5 Hz, 2CH2), 7.29 (d, 1H, J = 8.2 Hz, aromatic), 7.40 (dd, 1H, J = 1.8, 8.2 Hz, aromatic), 7.76 (dd, 2H, J = 2.0, 4.4 Hz, aromatic), 8.86 (dd, 2H, J = 2.0, 4.4 Hz, aromatic), 8.87 (d, 1H, J = 1.8 Hz, aromatic), 9.53 (s, 1H, NH).
With triethylamine; In dichloromethane; water; [Reference example 1-3B] Isonicotinoyl chloride hydrochloride (6.48 g, 36.4 mmol; commercial product) and triethylamine (5.57 mL, 54.6 mmol) were added sequentially at 0C to a dichloromethane (10 mL) solution of <strong>[1496-40-8]2-(1-piperidinyl)-5-(trifluoromethyl)aniline</strong> (4.45 g, 18.2 mmol) obtained in Reference example 1-2B. The mixture was stirred for 0.5 hours. Water was added to the mixture and then the mixture was subjected to extraction with ethyl acetate (x3). The thus obtained organic layer was washed with saturated sodium chloride solution, dried using anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate = 1/1) and recrystallization (hexane), so that N-[2-(1-piperidinyl)-5-(trifluoromethyl)phenyl]isonicotinamide (Compound 1) (5.49 g, 86.3%) was obtained as colorless solid.

  • 6
  • [ 39178-35-3 ]
  • [ 2247-88-3 ]
  • [ 1429342-56-2 ]
 

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Technical Information

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