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Structure of 1030613-07-0

Chemical Structure| 1030613-07-0

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Product Details of [ 1030613-07-0 ]

CAS No. :1030613-07-0
Formula : C5H5BrN2O2S
M.W : 237.07
SMILES Code : O=C(C1=NN=C(Br)S1)OCC
MDL No. :MFCD12165919
InChI Key :KDZLTNORBKZJKE-UHFFFAOYSA-N
Pubchem ID :52987824

Safety of [ 1030613-07-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1030613-07-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.4
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 0.0
Molar Refractivity 43.7
TPSA ?

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

80.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.99
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

1.94
Log Po/w (WLOGP)?

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

1.48
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.

0.43
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

2.5
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.67

Water Solubility

Log S (ESOL):?

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

-2.67
Solubility 0.506 mg/ml ; 0.00214 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.

-3.25
Solubility 0.133 mg/ml ; 0.000561 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

-2.26
Solubility 1.3 mg/ml ; 0.00547 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

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.

-6.37 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)

2.86

Application In Synthesis of [ 1030613-07-0 ]

* 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 [ 1030613-07-0 ]

[ 1030613-07-0 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 64837-53-2 ]
  • [ 1030613-07-0 ]
YieldReaction ConditionsOperation in experiment
87.4% With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 20 - 60℃; for 1.33333h; To a stirred solution of compound 59 (21 g, 121.38 mmol) in ACN (400 mL), CuBr2 (53.3 g, 239.01 mmol) was added and stirred at room temperature for 15 min. To this solution, tert- butyl nitrite (24.65 g, 239.04 mmol) was added drop wise over a period of 20 min. The resulting reaction mixture was stirred at room temperature for 30 min. and then heated at 60 C for 30 min. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water; ethyl acetate and filtered through Celite bed. The organic layer was separated; washed with brine; dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound 60 (25 g, 87.40percent) as a yellow solid. TLC: 20percent EtOAc/hexane (Rf: 0.7); 1H NMR (400 MHz, DMSO-d6): delta 4.45-4.40 (m, 2H), 1.34 (t, J= 6.8 Hz, 3H).
82% With hydrogen bromide; copper(I) bromide; sodium nitrite; In water; at 3 - 20℃; for 2.75h; A 500 mL (three neck) round-bottom flask with a stir bar, needle inlet, and a gas outlet to a trap containing a 10percent solution of Na2S203 was charged with CuBr (1.24g, 8.67 mmol, 0.1 equiv.) and HBr (48percent aqueous solution, 108 mL). The purple solution was cooled to 3°C (internal, ice bath), to which was added portion- wise a solid mixture of 5-amino-[l,3,4]thiadiazole-2-carboxylic acid ethyl ester (15.0 g, 86.6 mmol) and sodium nitrite (27.0 g, 391.3 mmol, 4.5 equiv.) over the course of 30 min. The reaction mixture was allowed to warm to room temperature for 2 h 15 min. The reaction mixture was diluted with CH2C12 and 10percent aqueous Na2S203 and the layers were separated. The aqueous layer was extracted 3 times with CH2C12. The combined organic layers were washed with Brine, dried over MgS04, and concentrated. The crude product was purified by column chromatography (ISCO XL, 330g Si02 column, 20-25percent EtOAc/Hexanes) to provide an off-white solid that was triturated with 5percent EtOAc/Hexanes. Filtration provided 5-bromo-[l ,3,4]thiadiazole-2-carboxylic acid ethyl ester (14.5 g, 71percent) as white needles. Concentration and trituration of the mother liquor provided an additional product (2.3 g, 11percent).
79% Step l:5-Bromo-[l,3,4]thiadiazole-2-carboxylic acid ethyl ester (3_39_2) [00332] CuBr2 (18.06 g, 80.1 mmol) was added to a suspension of 5-amino- [l,3,4]thiadiazole-2-carboxylic acid ethyl ester 3_39_1 (7 g, 40.5 mmol) in 150 mL of acetonitrile, the mixture was stirred for 15 min, t-BuONO (9.6 mL, 80.1 mmol) was added over 20 min., and the mixture was heated at 60°C for 0.5 h. Water and ethyl acetate were added, the mixture was stirred until the dark color disappeared and filtered through celite, and the organic layer was washed with brine, dried over Na2S04, filtrated and concentrated to give compound 3_39_2 (7.56 g, 79 percent yield) as a yellow solid. [00333] NMR (400 MHz, DMSO-d6): delta = 1.32 (t, J = 7.14 Hz, 3 H), 4.41 (q, J = 7.30 Hz, 2 H);
74% With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 20 - 60℃; for 0.666667h; Step 2: ethyl 5-bromo-l,3,4-thiadiazole-2-carboxylate ter-BuONOTo a stirred solution of ethyl 5-amino-l,3,4-thiadiazole-2-carboxylate (3.1 g, 17.8 mmol) in acetonitrile (50 mL) at room temperature was added copper (II) bromide (7.95 g, 35.6 mmol) and the mixture was stirred for 20 min. Tertiary butyl nitrite (3.67 g, 35.63 mmol) was then added drop wise for 10 min, and the reaction mixture was heated to 60°C for 30 min. The reaction mixture was concentrated under reduced pressure, diluted with water (300 mL), and then extracted with ethyl acetate (500 m:). The organic layer was separated and dried over anhydrous sodium sulphate, and evaporated to afford ethyl 5-bromo-l,3,4-thiadiazole-2-carboxylate as a brown solid (3.0 g, 74percent yield). XH NMR (400 MHz, CDC13): ? 4.53-4.51 (m, 2H), 1.45-1.43 (m, 3H); LC-MS m/z calcd for [M+H]+ 238.92, found 238.9.
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 20 - 60℃; for 1.08333h; Step 1: Ethyl 5-bromo-1,3,4-thiadiazole-2-carboxylate To a suspension of <strong>[64837-53-2]ethyl 5-amino-1,3,4-thiadiazole-2-carboxylate</strong> (10 g, 58 mmol) in CH3CN (180 mL) was added CuBr2 (25.7 g, 115 mmol). The mixture turned dark green and was further stirred for 15 min at room temperature. t-BuONO, 90percent (13.8 mL, 115 mmol) was added dropwise over 15-20 min. The mixture became slightly warm and gas was evolved after 5 min and then throughout the addition. After completion of the addition and gas evolution subsided, the mixture was heated at 60° C. for 30 min. Solvent was then evaporated in vacuo. Water and EtOAc were added and the mixture was agitated in the flask until the dark green color disappeared. The organic phase became light brown and the aqueous was green with insoluble material. The whole mixture was filtered through celite and washed with EtOAc. The EtOAc layer was separated, washed with dilute brine solution, dried (Na2SO4) and concentrated to give the title compound. 1H NMR (400 MHz, acetone-d6): delta4.52 (q, 2H), 1.43 (t, 3H).
To a suspension of ethyl 5-amino-l,3,4- thiadiazole-2-carboxylate in CH3CN (0.32 M) was added CuBr2 (2 equiv). The mixture turned dark green and was stirred for 15 min at room temperature. t-BuONO, 90percent (2 equiv) was added dropwise over 15 - 20 min. The mixture became slightly warm and gas evolved after about 5 min and then throughout the addition. After completion of the addition and after gas evolution subsided, the mixture was heated at 60 °C for 30 min. Solvent was then evaporated in vacuo. Water and EtOAc were added and the mixture was stirred until the dark green color disappeared. The organic phase became light brown and the aqueous phase was green with insoluble material. The entire mixture was filtered through Celite.(TM). and washed with EtOAc. The EtOAc layer was separated, washed with diluted brine, dried (Na2SO4) and concentrated to give the title compound. lH NMR (400 MHz, acetone-^): delta 4.52 (q, 2H), 1.43 (t, 3H).
To a suspension of ethyl 5-amino- l,3,4-thiadiazole-2-carboxylate in CH3CN (0.32 M) was added CuBr2 (2 equiv). The mixture turned dark green and was stirred for 15 min at room temperature. Then /-BuONO (2 equiv, 90percent) was added dropwise over 15 - 20 min. The mixture became slightly warm and gas evolved after about 5 min and then throughout the addition. After completion of the addition and after gas evolution subsided, the mixture was heated at 60 °C for 30 min. Solvent was then evaporated in vacuo. Water and EtOAc were added and the mixture was stirred until the dark green color disappeared. The mixture was filtered through Celite.(TM). and washed with EtOAc. The EtOAc layer was separated, washed with diluted brine, dried (Na2SO4) and concentrated to give the title compound. lH NMR (400 MHz, acetone-t/6): delta 4.52 (q, 2H), 1.43 (t, 3H).
Step 1 Ethyl 5-bromo-l ,3,4-thiadiazole-2-carboxylateTo a suspension of ethyl 5-ammo-l ,3,4-thiadiazole-2-carboxylate in CH3CN (0 32 M) was added CuBr2 (2 equiv) The mixture turned dark green and was stirred for 15 mm at room temperature ^-BuONO, 90percent (2 equiv) was added dropwise over 15 - 20 mm The mixture became slightly warm and gas was evolved after about 5 min and then throughout the addition After completion of the addition and gas evolution subsided, the mixture was heated at 60 0C for 30 mm Solvent was then evaporated under diminished pressure Water and EtOAc were added and the mixture was stirred until the dark green color disappeared The organic phase became light brown and the aqueous phase was green with insoluble material The entire mixture was filtered through celite and washed with EtOAc The EtOAc layer was separated, washed with diluted bpine, dpied (Na2SO4) and concentrated to give the title compound lH NMR (400 MHz, acetone-d) delta 4 52 (q, 2H), 1 43 (t, 3H)

 

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Technical Information

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