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Chemical Structure| 380380-64-3 Chemical Structure| 380380-64-3

Structure of 380380-64-3

Chemical Structure| 380380-64-3

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Product Details of [ 380380-64-3 ]

CAS No. :380380-64-3
Formula : C7H6BrN5
M.W : 240.06
SMILES Code : CN1N=C(C2=NC=C(Br)C=C2)N=N1
MDL No. :MFCD06796604
InChI Key :JANKGNBDRWYWSN-UHFFFAOYSA-N
Pubchem ID :23438653

Safety of [ 380380-64-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H228
Precautionary Statements:P240-P210-P241-P264-P280-P302+P352-P370+P378-P337+P313-P305+P351+P338-P362+P364-P332+P313
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 380380-64-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 11
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 50.01
TPSA ?

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

56.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

1.44
Log Po/w (WLOGP)?

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

1.03
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.

0.5
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

1.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.22

Water Solubility

Log S (ESOL):?

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

-2.8
Solubility 0.384 mg/ml ; 0.0016 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.

-2.23
Solubility 1.41 mg/ml ; 0.00586 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

-3.06
Solubility 0.211 mg/ml ; 0.000879 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.

-6.74 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

0.0
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)

2.31

Application In Synthesis of [ 380380-64-3 ]

* 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.

  • Upstream synthesis route of [ 380380-64-3 ]
  • Downstream synthetic route of [ 380380-64-3 ]

[ 380380-64-3 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 380380-64-3 ]
  • [ 856866-72-3 ]
YieldReaction ConditionsOperation in experiment
48% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; lithium chloride In N,N-dimethyl-formamide at 90℃; for 4 h; In a 100 ml reaction flask,Compound 7 (5.0 g, 10 mmol) and 50 ml of DMF were added,2- (1-methyl-tetrazol-5-yl) -5-bromopyridine (2.65, 11 mmol)Lithium chloride (1.7 g),1,1'-bis (diphenylphosphino) ferrocene] palladium chloride (1.0 g),The mixture was stirred at 90 ° C for 4 hours,After completion of the reaction,To room temperature,And extracted three times with water / ethyl acetate (V / V = 1: 1)The organic layers were combined,Dried over anhydrous sodium sulfate,And concentrated to give 1.7 g of the compound (1)The yield was 48percent
26% With lithium chloride In 1-methyl-pyrrolidin-2-one at 20 - 120℃; for 4 h; In 150ml of 1-methyl-2-pyrrolidone was dissolved 37g of (R)-3- (4- tributhylstannyl-3-fluorophenyl)-2-oxo-5-oxazolidinylmethanol. The solution was added with 19.7g of 2- (2-methyltetrazol-5-yl)-5-bromopyridine, 10.44g of lithium chloride and 2.9g of dichlorobistriphenylphospine palladium (I I) at room temperature and then stirred at the temperature of 120 C for 4 hours. The reaction mixture was added with water and then extracted with ethyl acetate. The organic layer, thus separated, was washed with brine, dehydrated, filtrated, concentrated in vacuo and purified by column chromatography to provide 8g of the title compound. Yield 26percent. 1H NMR (DMSO-d6) 5 8.90 (s, lH), 8. 18 (m, 2H), 7.70 (m, 2H), 7.49 (dd, 1H), 5.25 (t, 1H), 4.74 (m, 1H), 4.46 (s, 3H), 4.14 (t, lH), 3. 88 (dd, lH), 3.68 (m, lH), 3. 58 (m, lH)
26% With bis-triphenylphosphine-palladium(II) chloride; lithium chloride In 1-methyl-pyrrolidin-2-one at 120℃; for 4 h; Inert atmosphere To a solution of (R)-3-(4-tributhylstannyl-3-fluorophenyl)-2-oxo-5-oxazolidinylmethanol 5 (37.0 g, 74.0 mmol) in NMP (150 mL) was added 2-(2-methyltetrazol-5-yl)-5-bromopyridine 9 (19.7 g, 81.9 mmol), LiCl (10.4 g, 245 mmol) and Pd(PPh3)2Cl2 (2.90 g, 4.13 mmol). The reaction mixture was stirred for 4 h at 120 °C. After being cooled to room temperature, the reaction mixture was poured into water and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was further purified by column chromatography to obtain the title compound (8 g, 26percent). Mp: 201 °C. 1H NMR (DMSO-d6): δ 8.90 (s, 1H), 8.18 (m, 2H), 7.70 (m, 2H), 7.49 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 5.25 (t, J = 5.6 Hz, 1H), 4.74 (m, 1H), 4.46 (s, 3H), 4.14 (t, J = 8.8 Hz, 1H), 3.88 (m, 1H), 3.68 (m, 1H), 3.58 (m, 1H). 13C NMR (DMSO-d6): δ 163.56, 159.03, 154.06, 149.18, 144.78, 140.30, 136.96, 131.42, 130.73, 121.89, 118.36, 113.81, 105.18, 73.39, 61.52, 45.96, 39.63. IR (neat, cm-1): 3251.40, 1746.23, 1619.91, 1473.35, 1406.82. [M + H]+: 371.02. HRMS [EI-MS]: m/z, calculated for [C17H15FN6O3] 370.1190, found, 370.1100 [C17H15FN6O3].
References: [1] Patent: CN105859780, 2016, A, . Location in patent: Paragraph 0038.
[2] Patent: WO2005/58886, 2005, A1, . Location in patent: Page/Page column 28; 29.
[3] European Journal of Medicinal Chemistry, 2011, vol. 46, # 4, p. 1027 - 1039.
[4] Patent: CN107400126, 2017, A, . Location in patent: Paragraph 0036.
  • 2
  • [ 444335-16-4 ]
  • [ 380380-64-3 ]
  • [ 856866-72-3 ]
YieldReaction ConditionsOperation in experiment
83%
Stage #1: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; bis(pinacol)diborane In dimethyl sulfoxide at 80℃; for 14 h; Inert atmosphere
Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate In 1,4-dioxane; water at 70℃; for 3 h; Inert atmosphere
DMSO (100 ml) was added to a 250 ml reaction flask,(5R) -3- (4-bromo-3-fluorophenyl) -5-hydroxymethyloxazolidin-2-one(10 g, 34.5 mmol), pinacolate (17.52 g, 69 mmol),[1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium dichloromethane complex (1.41 g, 1.73 mmol)And potassium acetate (13.5 g, 138 mmol), and the temperature was raised to 80 ° C under a nitrogen atmosphere,For 14 hours. The heating was stopped, the solution was cooled to room temperature, and extracted with water / ethyl acetate 3 times. The organic layers were combined and the organic layer was washed with saturated waterBrine, dried over anhydrous sodium sulfate and concentrated by suction filtration. The concentrated product of the above step was added to a 250 ml reaction flask,1,4-dioxane (100 ml) was added,5-bromo-2- (2-methyl-2H-tetrazol-5-yl) pyridine(8.28 g, 34.5 mmol),[1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium dichloromethane complex (0.56 g, 0.69 mmol)And cesium carbonate aqueous solution (50 ml, containing 33.72 g of cesium carbonate, 103.5 mmol),Under nitrogen protection,The temperature was raised to 70 ° C,The reaction was carried out for 3 hours,Dichloromethane was added for extraction.The separated organic phase was washed with saturated brine,Anhydrous sodium sulfate dehydration,filter,Concentrated in vacuo and purified by column chromatography,10.6 g of a solid was obtained,The yield was 83.0percentHPLC purity was 98.34percent (area normalization method).
References: [1] Patent: CN105418678, 2016, A, . Location in patent: Paragraph 0070; 0071; 0072; 0073; 0074; 0075.
  • 3
  • [ 380380-64-3 ]
  • [ 856866-72-3 ]
References: [1] Chemical and Pharmaceutical Bulletin, 2015, vol. 63, # 2, p. 143 - 146.
 

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