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Chemical Structure| 363-51-9 Chemical Structure| 363-51-9

Structure of 2-Chloro-6-fluoroaniline
CAS No.: 363-51-9

Chemical Structure| 363-51-9

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Product Details of [ 363-51-9 ]

CAS No. :363-51-9
Formula : C6H5ClFN
M.W : 145.56
SMILES Code : C1=C(C(=C(C=C1)Cl)N)F
MDL No. :MFCD00040309
InChI Key :ZJLAWMDJTMMTQB-UHFFFAOYSA-N
Pubchem ID :2734205

Safety of [ 363-51-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 363-51-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 35.81
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.

1.68
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.

2.49
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.

2.51
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

2.21
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.24

Water Solubility

Log S (ESOL):?

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

-2.68
Solubility 0.305 mg/ml ; 0.0021 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 0.489 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

-2.91
Solubility 0.179 mg/ml ; 0.00123 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.

-5.56 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

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)

1.39

Application In Synthesis of [ 363-51-9 ]

* 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 [ 363-51-9 ]

[ 363-51-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 363-51-9 ]
  • [ 13321-74-9 ]
  • [ 1432270-44-4 ]
YieldReaction ConditionsOperation in experiment
46% With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 160℃; for 3h;Inert atmosphere; Microwave irradiation; General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2).
  • 2
  • [ 363-51-9 ]
  • [ 2972-52-3 ]
  • 2,4-dichloro-N-(2-chloro-6-fluorophenyl)pyrimidine-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% In tetrahydrofuran; at 20℃; for 15h;Inert atmosphere; To a solution of PE1-028-B2 acid chloride (6.36 g, 0.030 mol) obtained in the previous step in THF (40 mL) under inert conditions, 2-chloro-6-fluoroaniline (4.38 g, 0.03 mol) was addedportion wise and the reaction mixture was stirred at r.t. for 15 h. The resulting precipitate was filtered, washed with DCM (15 mL) and the solid obtained was sonicated in HC1 (1M, 100 mL), filtered and washed with water (20 mL), DCM (20 mL) sequentially and dried under high vacuum to obtain the title compound 7c (5.529 g) as a white solid. The first filtrate (i.e., THF and DCM) was concentrated, slurried with DCM (15 mL) and filtered to get a solid. The solidwas again sonicated with HC1 (1M, 30 mL), filtered and washed with water (20 mL), DCM (15 mL) sequentially and dried under high vacuum to obtain another crop of pure product 7c (1.702 g) also as a white solid. The combined yield of 7c (7.23 1 g, 75%), mp 207-211 C. ‘H NMR (400 MHz, DMSO-d6): ö 10.71 (s, 1H), 9.03 (s, 1H), 7.48-7.36 (m, 3H); ‘9F NMR (376 MHz, DMSOd 6): -115.25, -115.28 (m); LC-MS (ESI+) m/z 319.96 (M+H) HRMS (ESI+) m/z calculated forC,,H6C13FN3O (M+H) 319.9555, found 319.9562.
  • 3
  • [ 397308-78-0 ]
  • [ 363-51-9 ]
  • N-(2-chloro-6-fluoro-phenyl)-4-hydroxy-2-methylsulfanyl-pyrimidine-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
52.8% A stirred solution of 9 <strong>[397308-78-0]4-hydroxy-2-methylsulfanyl-pyrimidine-5-carboxylic acid</strong> (5.70 g, 30.65 mmol, 1.0 eq) and 237 2-chloro-6-fluoro-aniline (4.50 g, 30.65 mmol, 1.0 eq) in 24 toluene (200 mL) was purged with nitrogen gas for 15 min. To the above solution 91 PCl3 (30 mL) was added. The reaction was heated at 100 C. for 72 h. Progress of reaction was monitored by LCMS. After completion of reaction, solvent was removed under reduced pressure, residue was diluted with a mixture of 238 diethyl ether: 30 MeOH (10:1) (100 mL) stirred for 15 min then filtered off. Solid was suspended in MeOH (20 mL), stirred for 5 min, filtered off and washed with MeOH (10 mL), and then dried under vacuum to obtain of 239 N-(2-chloro-6-fluoro-phenyl)-4-hydroxy-2-methylsulfanyl-pyrimidine-5-carboxamide (5.0 g, 52.8%). (0370) LCMS: 314 [M+1]+
 

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