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Chemical Structure| 175358-01-7

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Product Details of [ 175358-01-7 ]

CAS No. :175358-01-7
Formula : C6H6ClN3O
M.W : 171.58
SMILES Code : O=C(N)C1=NC(Cl)=CC=C1N
MDL No. :MFCD09750671
InChI Key :ZGGQDDSXBIALBC-UHFFFAOYSA-N
Pubchem ID :10749704

Safety of [ 175358-01-7 ]

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

Computational Chemistry of [ 175358-01-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 41.75
TPSA ?

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

82.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.34
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

-0.35
Log Po/w (WLOGP)?

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

0.42
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.

-0.39
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

0.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.09

Water Solubility

Log S (ESOL):?

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

-1.02
Solubility 16.4 mg/ml ; 0.0953 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.

-0.91
Solubility 21.1 mg/ml ; 0.123 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

-1.87
Solubility 2.33 mg/ml ; 0.0136 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

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.

-7.6 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)

1.73

Application In Synthesis of [ 175358-01-7 ]

* 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 [ 175358-01-7 ]

[ 175358-01-7 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 122-51-0 ]
  • [ 175358-01-7 ]
  • [ 171178-33-9 ]
YieldReaction ConditionsOperation in experiment
80% at 140℃; for 2h; Add 3 (2.5g, 14.6mmol) and triethyl orthoformate (100mL, 60mmol) in a 250mL eggplant-shaped bottle, react at 140 for 2h, complete reaction by TLC, cool to room temperature, filter to obtain filter cake, and dry to light yellow Solid 2.1g, yield 80%.
72% for 3h;Heating / reflux; A suspension of e-chloro^-carboxamido-S-amino-pyridine (1.34 mmol, 230 mg) in triethyl orthoformate (10 ml) was refluxed for 3 hours. A white suspension was formed which was cooled down to room temperature. The precipitate was filtered off and dried under vacuum resulting in the pure title compound (174 mg, yield 72 %) which was characterised by its mass spectrum as follows: MS (m/z) : 182, 184([M+H]+, 100).
42% With acetic anhydride; for 2h;Reflux; Acetic anhydride (15.1 mL, 160 mmol) was added to a mixture of 3-amino-6-chloro- pyridine-2-carboxamide (2.50 g, 14.6 mmol) and triethyl orthoformate (15.1 mL, 90.7 mmol). The reaction mixture was refluxed for 2 hours and it was cooled down to 20C which caused the formation of a precipitate. Isopropanol (20 mL) was added and the solid was filtered, washed with isopropanol and dried under vacuum to afford 6-chloropyrido[3,2-d]pyrimidin- 4(3H)-one (1.10 g, 6.06 mmol, 42% yield) as a beige solid. LCMS [M+H+] 182.0.
at 145℃; for 3h; a) Method for synthesising P-2a:; Cl theta-chloro^-cyano-S-nitropyridine (9.50 g, 51.76 mmol) is taken up in 150 ml. of 90 % H2SO4 solution. The reaction mixture is stirred for 4 h at 70 0C, cooled and slowly added dropwise to ice water. The precipitate formed is filtered off, washed with water and dried. The aqueous filtrate is extracted 6 x with DCM. The organic phases are combined, dried on Na2SO4, filtered off and concentrated by rotary evaporation. The residue is mixed with the precipitate, dried overnight at 50 0C in the drying cupboard and 6-chloro-3-nitro- pyridine-2-carboxylic acid amide (HPLC-MS: tRet = 0.43 min; MS (M+H)+ = 202) is obtained. theta-chloro-S-nitro-pyridine^-carboxylic acid amide (10.43 g, 51.75 mmol) is taken up in EtOH (250 ml_), combined with ammonium chloride (1.384 g, 25.87 mmol) in water(250 ml.) and heated to 60 0C. At this temperature iron powder (8.67 g, 155.23 mmol) is added batchwise and the mixture is stirred for 1 h at 60 0C. After cooling it is concentrated by rotary evaporation, filtered through silica gel, washed with DCM/MeOH (90/10 to 80/20), the resulting filtrate is evaporated down using the rotary evaporator and 3-amino- theta-chloro-pyridine^-carboxylic acid amide (HPLC-MS: tRet = 0.90 min; MS (M+H)+ = 172) is obtained.S-amino-theta-chloro-pyridine^-carboxylic acid amide (7.45 g, 43.41 mmol) is taken up in triethylorthoformate (150 mL) and stirred for 3 h at 145 0C. After cooling the precipitate formed is filtered off, washed with Et2O, dried and 6-chloro-3/-/-pyrido[3,2-d]pyrimidin-4- one (HPLC-MS: tRet = 0 min; MS (M+H)+ = 182) is obtained.6-chloro-3/-/-pyrido[3,2-d]pyrimidin-4-one (7.16 g, 39.43 mmol) and Lambda/,Lambda/-diethylaniline (9.505 mL, 59.14 mmol) are taken up in toluene (185 mL) and heated to 110 0C. Then POCI3 (3.713 mL, 39.43 mmol) is slowly added dropwise. The reaction mixture is stirred for a further 4 h at 110 0C. After cooling the mixture is diluted with toluene, washed 2 x with water, 2 x with 20 % NaOH solution and 1 x with 1 M HCI solution. The organic phase is dried on MgSO4, filtered off, evaporated down and P-2a is obtained (HPLC-MS: tRet = 1.14 min).Method of synthesis from: J. Med. Chem. 1996, 39, 1823-1835.

  • 2
  • [ 171178-21-5 ]
  • [ 175358-01-7 ]
YieldReaction ConditionsOperation in experiment
92% With iron; ammonium chloride; In ethanol; water; at 60℃; for 1.0h; Pyridine Z.5 (2.00 g, 1 0.0 mmol) and iron filings (2.77 g, 49.6 mol) are taken up in EtOH/H20 (100 mL, 1 :1 ), combined with NH4CI (265 mg, 4.91 mmol) and heated to 60C for 1 h. The solvent is removed, the residue is taken up in DCM/MeOH (50 mL, 9:1 ), filtered through Celite, the solvent is eliminated again and pyridine Z.6 (1 .57 g, 92 %) is obtained.
92% With iron; ammonium chloride; In ethanol; water; at 60℃; for 1.0h; Method of Synthesising the Azaquinazolines D*.2 and D.2Pyridine ED.4 (10.0 g, 54.5 mmol) is taken up in H2SO4 (150 mL, 90%) and heated to 70 C. for 3.5 h. Then the reaction mixture is cooled to 20 C., added dropwise to ice water, the precipitate is filtered off, washed with H2O, dried and pyridine Z.5 (10.5 g, 95%) is obtained.Pyridine Z.5 (2.00 g, 10.0 mmol) and iron filings (2.77 g, 49.6 mol) are taken up in EtOH/H2O (100 mL, 1:1), combined with NH4Cl (265 mg, 4.91 mmol) and heated to 60 C. for 1 h. The solvent is removed, the residue is taken up in DCM/MeOH (50 mL, 9:1), filtered through Celite, the solvent is eliminated again and pyridine Z.6 (1.57 g, 92%) is obtained.Pyridine Z.6 (500 mg, 2.91 mmol) is taken up in triethylorthoformate (10 mL) and heated to 145 C. for 18 h. Then the reaction mixture is cooled to 20 C., the precipitate is filtered off, washed with Et2O (10 mL), dried and azaquinazolone Z.7 (433 mg, 82%) is obtained.Azaquinazolone Z.7 (200 mg, 1.10 mmol) is placed in toluene (5.0 mL), combined with N,N-diethylaniline (0.27 mL) and POCl3 (0.88 mL) and heated to 110 C. for 4 h. The reaction mixture is cooled to 20 C., diluted with toluene (5 mL) and H2O (5 mL), washed with NaOH (3×10 mL, 20%) and HCl (2×10 mL, 1 M), dried on Na2SO4, filtered, freed from the solvent and azaquinazoline D*.2 (165 mg, 75%) is obtained.Azaquinazoline D*.2 (1.15 g, 5.75 mmol) is placed in DCM (5.0 mL), cooled to 0 C., combined with methylamine (3.5 mL, 7.19 mmol, 2 M in THF) and DIPEA (3.0 mL), the reaction mixture is heated to 20 C. and stirred for 1 h at 20 C. The solvent is removed, the residue is taken up in H2O, the precipitate is filtered off, washed with H2O and azaquinazoline D.2 (640 mg, 57%; HPLC-MS: MS (M+H)+=195; tRet.=1.85 min; method 1_BAS).
89% With palladium 10% on activated carbon; hydrogen; In ethyl acetate; at 20℃; for 3.0h; 6-Chloro-3-nitropicolinamide, 4.80 g (23.8 mmol), and palladium carbon (10%), 0.67 g (6.3 mmol), were added into 60 ml_ of ethyl acetate. The resulting mixture was stirred under hydrogen atmosphere (2 atm) for 3 hours at room temperature. Then palladium on carbon was filtered out and washed with ethyl acetate. The solvent was removed in vacuo to give 3.79 g (89%) of the product as a yellow solid. MS (ESIpos): m/z = 172 (M+H)+; LC-MS (Method 4, Acetonitrile-Water-0.1 % FA-10%B): Rt = 0.59 min.
With iron; ammonium chloride; In ethanol; water; at 60℃; for 1.0h; a) Method for synthesising P-2a:; Cl theta-chloro^-cyano-S-nitropyridine (9.50 g, 51.76 mmol) is taken up in 150 ml. of 90 % H2SO4 solution. The reaction mixture is stirred for 4 h at 70 0C, cooled and slowly added dropwise to ice water. The precipitate formed is filtered off, washed with water and dried. The aqueous filtrate is extracted 6 x with DCM. The organic phases are combined, dried on Na2SO4, filtered off and concentrated by rotary evaporation. The residue is mixed with the precipitate, dried overnight at 50 0C in the drying cupboard and 6-chloro-3-nitro- pyridine-2-carboxylic acid amide (HPLC-MS: tRet = 0.43 min; MS (M+H)+ = 202) is obtained. theta-chloro-S-nitro-pyridine^-carboxylic acid amide (10.43 g, 51.75 mmol) is taken up in EtOH (250 ml_), combined with ammonium chloride (1.384 g, 25.87 mmol) in water(250 ml.) and heated to 60 0C. At this temperature iron powder (8.67 g, 155.23 mmol) is added batchwise and the mixture is stirred for 1 h at 60 0C. After cooling it is concentrated by rotary evaporation, filtered through silica gel, washed with DCM/MeOH (90/10 to 80/20), the resulting filtrate is evaporated down using the rotary evaporator and 3-amino- theta-chloro-pyridine^-carboxylic acid amide (HPLC-MS: tRet = 0.90 min; MS (M+H)+ = 172) is obtained.S-amino-theta-chloro-pyridine^-carboxylic acid amide (7.45 g, 43.41 mmol) is taken up in triethylorthoformate (150 mL) and stirred for 3 h at 145 0C. After cooling the precipitate formed is filtered off, washed with Et2O, dried and 6-chloro-3/-/-pyrido[3,2-d]pyrimidin-4- one (HPLC-MS: tRet = 0 min; MS (M+H)+ = 182) is obtained.6-chloro-3/-/-pyrido[3,2-d]pyrimidin-4-one (7.16 g, 39.43 mmol) and Lambda/,Lambda/-diethylaniline (9.505 mL, 59.14 mmol) are taken up in toluene (185 mL) and heated to 110 0C. Then POCI3 (3.713 mL, 39.43 mmol) is slowly added dropwise. The reaction mixture is stirred for a further 4 h at 110 0C. After cooling the mixture is diluted with toluene, washed 2 x with water, 2 x with 20 % NaOH solution and 1 x with 1 M HCI solution. The organic phase is dried on MgSO4, filtered off, evaporated down and P-2a is obtained (HPLC-MS: tRet = 1.14 min).Method of synthesis from: J. Med. Chem. 1996, 39, 1823-1835.

 

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