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Structure of 944805-17-8

Chemical Structure| 944805-17-8

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Product Details of [ 944805-17-8 ]

CAS No. :944805-17-8
Formula : C9H11BrN2O3S
M.W : 307.16
SMILES Code : O=C(OC(C)(C)C)NC1=NC(Br)=C(C=O)S1
MDL No. :MFCD18836517
InChI Key :JYXJVZYNONJDLM-UHFFFAOYSA-N
Pubchem ID :45117881

Safety of [ 944805-17-8 ]

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

Computational Chemistry of [ 944805-17-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 5
Fraction Csp3 0.44
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 65.45
TPSA ?

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

96.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.11
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

2.67
Log Po/w (WLOGP)?

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

2.87
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.

0.78
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

2.71
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.23

Water Solubility

Log S (ESOL):?

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

-3.33
Solubility 0.144 mg/ml ; 0.00047 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.

-4.35
Solubility 0.0138 mg/ml ; 0.0000448 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-3.03
Solubility 0.285 mg/ml ; 0.000929 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

Yes
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.

-6.28 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

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<0.0
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)

3.08

Application In Synthesis of [ 944805-17-8 ]

* 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 [ 944805-17-8 ]

[ 944805-17-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 68-12-2 ]
  • [ 405939-39-1 ]
  • [ 944805-17-8 ]
YieldReaction ConditionsOperation in experiment
70% To a solution of diisopropylamine (3.3 mL, 23 mmol) in THF (20. mL) at 0 C was added n-butyllithium (14.8 mL, 1.6 M in hexanes) slowly. The reaction was stirred for 20 minutes and then tert- butyl (5- bromothiazol-2-yl)carbamate (2.00 g, 7.16 mmol) was added slowly as a solution in THF (20. mL). The mixture was stirred for 30 minutes at 0 C and then DMF (1.8 mL, 23 mmol) was added. The solution was stirred for 2h at rt. EA and water were added, the layers were separated, and the organics were washed with brine. The organics were dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography using ethyl acetate in heptane as eluent to yield the title compound (1.53 g,70% yield). LCMS (ESI): [M+H] 308.9 for 81Br. 1HNMR: (400 MHz, Methanol- 4) d 9.83 (s, 1H), 1.56 (s, 9H).
64% Example 18, Step F[00180] To (i-Pr)2NH (59.7 g, 0.591 mol) in THF (250 mL) at 0C was added n-BuLi (236 mL, 2.5 M, 0.591 mol) was added slowly. The reaction mixture was stirred for 20 mins after which a THF solution of compound 15_2 (50 g, 0.179 mol) was slowly added to the reaction mixture with continued stirring. The mixture was stirred for 30 mins at 0C and then DMF (43.1 g, 0.591 mol) added. The mixture was stirred for 12 hrs at r.t. and diluted with EtOAc and water. The organic layer was separated, washed with brine, dried over Na2S04 and concentrated in vacuo. The residue was purified by silica chromatography to give compound 18_1 (35 g, 64%) as a white solid. [00181] This compound was characterized by proton NMR (1HNMR) in accordance with the procedures described herein. Proton NMR yielded the following results: 1H NMR (DMSO-d6, 400MHz): delta 9.73(s, 1 H); 1.47(s, 9H).
64% Example 18, Step F[00180] To (i-Pr)2NH (59.7 g, 0.591 mol) in THF (250 mL) at 0C was added n-BuLi (236 mL, 2.5 M, 0.591 mol) was added slowly. The reaction mixture was stirred for 20 mins after which a THF solution of compound 15_2 (50 g, 0.179 mol) was slowly added to the reaction mixture with continued stirring. The mixture was stirred for 30 mins at 0C and then DMF (43.1 g, 0.591 mol) added. The mixture was stirred for 12 hrs at r.t. and diluted with EtOAc and water. The organic layer was separated, washed with brine, dried over Na2S04 and concentrated in vacuo. The residue was purified by silica chromatography to give compound 18_1 (35 g, 64%) as a white solid. [00181] This compound was characterized by proton NMR (1HNMR) in accordance with the procedures described herein. Proton NMR yielded the following results: 1H NMR (DMSO-d6, 400MHz): delta 9.73(s, 1 H); 1.47(s, 9H).
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Ester Cleavage • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reactions with Organometallic Reagents • Reformatsky Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Stetter Reaction • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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