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Structure of 50735-34-7

Chemical Structure| 50735-34-7

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Product Details of [ 50735-34-7 ]

CAS No. :50735-34-7
Formula : C7H7BrN2O2
M.W : 231.05
SMILES Code : NC1=NC=C(C=C1C(=O)OC)Br
MDL No. :MFCD04117787
InChI Key :POWKBBOOIZBIRZ-UHFFFAOYSA-N
Pubchem ID :2763453

Safety of [ 50735-34-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 50735-34-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 47.62
TPSA ?

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

65.21 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.6
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

1.6
Log Po/w (WLOGP)?

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

1.22
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.

0.91
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

1.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.3

Water Solubility

Log S (ESOL):?

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

-2.52
Solubility 0.7 mg/ml ; 0.00303 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.

-2.58
Solubility 0.606 mg/ml ; 0.00262 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

-2.6
Solubility 0.578 mg/ml ; 0.0025 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.

-6.57 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)

1.76

Application In Synthesis of [ 50735-34-7 ]

* 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.

  • Upstream synthesis route of [ 50735-34-7 ]
  • Downstream synthetic route of [ 50735-34-7 ]

[ 50735-34-7 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 14667-47-1 ]
  • [ 50735-34-7 ]
YieldReaction ConditionsOperation in experiment
99% With bromine; sodium hydrogencarbonate In dichloromethane at 0 - 20℃; for 1 h; To a stirred solution of 2-amino-nicotinic acid methyl ester (2 g, 13.15 mmol) and sodium bicarbonate (2.2 g, 26.31 mmol) in DCM (30 mL) is added a solution of bromine (1.01 mL in DCM (20 mL) drop wise at 0° C.
The reaction mixture is stirred at room temperature for 1 hour.
The reaction mixture is quenched with sodium bisulfite solution (50 mL) and extracted with DCM (2*40 mL).
The combined organic layers are washed with brine (40 mL), dried over sodium sulphate, filtered, and evaporated under reduced pressure to give the title compound as a yellow solid (3 g, 99percent). LCMS m/z (79Br/81Br) 231/233 (M+H)+.
References: [1] Patent: US2017/29420, 2017, A1, . Location in patent: Paragraph 0034.
  • 2
  • [ 67-56-1 ]
  • [ 52833-94-0 ]
  • [ 50735-34-7 ]
YieldReaction ConditionsOperation in experiment
94% at 80℃; for 18 h; Inert atmosphere To a solution of 2-amino-5-bromonicotinic acid 22 (1.0 g, 4.6 mmol)in MeOH (10 mL) was added sulphuric acid (2.0 mL, 36.8 mmol)dropwise and the mixture was stirred at 80 °C for 18 h. After completionmonitored by TLC, the solvent was removed under reduced pressure.The residue was neutralised with sat. NaHCO3 (aq.) and extracted withethyl acetate (3×20 mL). The combined organic layers were driedover MgSO4 and concentrated in vacuo to afford the product 23 as awhite powder (1.0 g, 94percent) without further purification. m.p.148–149 °C; Rf (CH2Cl2/MeOH 20:1): 0.55; 1H NMR (400 MHz, d6-DMSO): δ 8.24 (1H, d, J=2.4 Hz), 8.21 (1H, d, J=2.4 Hz), 6.68–6.19(2H, br.s), 3.89 (3H, s); 13C NMR (100 MHz, d6-DMSO): δ 166.6, 158.0,154.4, 142.0, 107.5, 106.1, 52.4. HRMS (ESI+) Calc. for C7H7N2O2Br [M+H]+ 230.9764/232.9743, found 230.9765/232.9745. IR (neat,cm−1): v 3425, 3131, 2918, 1704, 1620, 1223, 796, 526.
63%
Stage #1: for 0.25 h; Cooling with ice
Stage #2: at 80℃; for 8 h; Inert atmosphere
Compound 1 (27.40 g, 126.88 mmol) obtained in Step 1 of Example 1 was placed in a well-dried 1000 mL three-neck round bottom flask and placed in a water bath containing ice water. 250 mL of methanol was added and stirred for 15 minutes. Sulfuric acid (125.80 mL, 2360.00 mmol) was slowly added dropwise thereto. The mixture was stirred for 8 hours at a temperature of 80 ° C under a stream of nitrogen. The product was poured into 1500 mL of ice water and neutralized with NaHCO 3 until the pH reached 7. Extraction with dichloromethane followed by column separation with 100percent dichloromethane. The resulting solid was dried to give compound 2 (18.5 g, 63percent yield).
References: [1] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 22, p. 5852 - 5869.
[2] Patent: KR2018/82356, 2018, A, . Location in patent: Paragraph 0154; 0159-0161.
  • 3
  • [ 67-56-1 ]
  • [ 52963-33-4 ]
  • [ 50735-34-7 ]
YieldReaction ConditionsOperation in experiment
36% at 75℃; for 48 h; 2. To a suspension of 2-amino-5-bromonicotinic acid hydrobromide (18.8 g, 60.0 mmol) in 150 mL of methanol was added cone, sulfuric acid (6 mL). The mixture was heated at 75 °C for 2 days, evaporated, diluted with water (100 mL), basified with solid sodium bicarbonate to pH 7-8, and extracted with ethyl acetate (3 x 100 mL). The extracts were washed with brine (50 mL), dried over sodium sulfate and filtered. The filtrate was dried in vacuo and the residue was purified by flash chromatography eluted with ethyl acetate/hexanes (1/4) to afford methyl 2-amino-5- bromonicotinate as a white solid in 36percent yield (5.0 g). 1H NMR (400 MHz, CDC13): δ 8.26 (d, J= 2.8 Hz, 1H), 8.23 (d, J= 2.8 Hz, 1H), 3.92 (s, 3H).
References: [1] Patent: WO2015/81257, 2015, A2, . Location in patent: Page/Page column 65-66.
  • 4
  • [ 52833-94-0 ]
  • [ 18107-18-1 ]
  • [ 50735-34-7 ]
References: [1] Patent: WO2007/67416, 2007, A2, . Location in patent: Page/Page column 111.
  • 5
  • [ 5345-47-1 ]
  • [ 50735-34-7 ]
References: [1] Patent: WO2015/81257, 2015, A2, .
[2] Patent: KR2018/82356, 2018, A, .
[3] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 22, p. 5852 - 5869.
 

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